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  • 201
    Electronic Resource
    Electronic Resource
    Changes in the extracellular levels of glutamate and aspartate during ischemia and hypoglycemia Effects of hypothermia (1998)
    Springer
    Experimental brain research 121 (1998), S. 277-284 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemia ; Hypothermia ; Microdialysis ; Ischemia ; Transmitter release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hypothermia (33° C) dramatically diminishes ischemic but not hypoglycemic brain damage. The beneficial effects of hypothermia in ischemia have been partly attributed to a reduction in the ischemia-induced increase in synaptic levels of glutamate or aspartate. With the microdialysis technique, we studied the effects of hypothermia (33° C) on the brain extracellular levels of glutamate and aspartate during hypoglycemia, ischemia, and their combination. In isoelectric hypoglycemia, striatal levels of glutamate and aspartate frequently show large transients of transmitter release occurring during both normothermia and hypothermia, whereas in the cortex levels of glutamate and aspartate are slightly lower during hypothermia compared with normothermia. In both regions studied, complete ischemia induced by i.v. KCl results in a progressive increase in glutamate and aspartate levels over time. In normoglycemic animals, hypothermia markedly attenuates the increase in glutamate and aspartate levels in the striatum but not in the cortex. Also in hypoglycemic animals, complete ischemia causes a progressive increase in the glutamate and aspartate levels. However, hypothermia affects only striatal glutamate levels. Since hypothermia protects both cortex and striatum against ischemic brain injury and not against hypoglycemic injury, presumably the protective effect of hypothermia is due to factors other than prevention of glutamate or aspartate overflow.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050461
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  • 202
    Electronic Resource
    Electronic Resource
    Time-course expression of vascular endothelial growth factor as related to the development of the retinochoroidal vasculature in rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 155-160 
    Details
    ISSN: 1432-1106
    Keywords: Key words Retinochoroidal vasculature ; Retinal pigment epithelium ; Vascular endothelial growth factor ; In situ hybridization ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Growth factors involved in angiogenesis are critical to both the normal and pathological vascular development in the retina and choroid. In the present experiment, the relationship between the vascular endothelial growth factor (VEGF) expression and the retinochoroidal vasculogenesis in Sprague-Dawley rats was investigated using in situ hybridization and immunohistochemistry. It was found that VEGF was produced mainly by astrocytes and Müller cells in the neural retina, and this was correlated temporally and spatially with the retinal vasculogenesis. In addition, it was observed that, although the VEGF expression in the retinal pigment epithelium (RPE) decreased with increasing age, it persisted from the embryonic stage to adulthood. These findings indicate that the VEGF expression in RPE may play a role in the development of the choroidal vessels as well as in the maintenance of the normal structure and permeability of the choriocapillaris in adults.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050267
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  • 203
    Electronic Resource
    Electronic Resource
    Ascending propriospinal afferents to area X (substantia grisea centralis) of the spinal cord in the rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 356-366 
    Details
    ISSN: 1432-1106
    Keywords: Key words Spinal cord ; Central canal ; Substantia grisea centralis ; Propriospinal afferents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Area X (the tenth area) of the spinal cord is a region surrounding the central canal and extending throughout the spinal cord length. Using anterograde and retrograde labeling techniques, ascending propriospinal projections to area X were examined in the rat. For anterograde tracing of axons, biotinylated dextran was injected into middle-thoracic, lumbar, or sacral-caudal segments. Unilateral injections resulted in bilateral labeling of terminals in area X of all segments rostral to the injections. The distribution of labeled terminals was conspicuous in regions dorsal and lateral to the central canal. The labeled axons were derived from the ventrolateral and the lateral cord. They coursed through lamina VII, giving off terminal axons. While giving off terminal axons in area X, they coursed further rostrally or caudally along the central canal or crossed over the central canal to terminate in the contralateral area X. Possible cells of origin of these ascending afferents were examined after injections of wheat germ agglutinin-horseradish peroxidase into regions surrounding the central canal (area X) at the cervical or thoracic level. Retrogradely labeled neurons were consistently seen in area X, and laminae VII and VIII of the thoracic and lumbar segments. The present study shows that ascending propriospinal axons project to area X of all spinal levels rostral to the cells of origin and suggests that some of these afferents may originate from neurons in area X and laminae VII and VIII. Based on previous data, it is surmised that area X functions, through these intricate interconnections, as a site for integration or modulation of somatic or nociceptive and visceroceptive sensation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050351
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  • 204
    Electronic Resource
    Electronic Resource
    Do non-dopaminergic neurons in the ventral tegmental area play a role in the responses elicited in A10 dopaminergic neurons by electrical stimulation of the prefrontal cortex? (1998)
    Springer
    Experimental brain research 118 (1998), S. 466-476 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular recording ; Cortical efferents ; A10 cell group ; Non-dopaminergic neurons ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  It is rapidly becoming apparent that the prefrontal cortex (PFC) plays a major role in controlling the activity of midbrain dopaminergic (DA) neurons. We have previously demonstrated that electrical stimulation of the PFC elicits inhibition-excitation (IE) and excitation (E) activity patterns in DA neurons in the ventral tegmental area (VTA; A10 cell group). Since non-DA neurons in the VTA are cortically innervated, synapse upon DA neurons and appear to have an inhibitory impact, we determined the extent to which the responses of these neurons to stimulation of the PFC could account for the responses seen in DA neurons upon cortical stimulation. Stimulation of the PFC (0.25 mA and 1.0 mA) elicited three categories of response in the majority of VTA non-DA neurons. Types I and II were characterised by a short-to-moderate latency excitation (referred to as “early excitations”), in the latter case preceded by inhibition. Type III responses consisted of inhibition in the absence of an early excitation. Elements of these responses were compared with the temporal characteristics of key elements of responses elicited in DA neurons by PFC stimulation. Although the early excitations in non-DA neurons preceded the inhibitions in DA neurons exhibiting IE responses, the early excitations began approximately 100 ms before the inhibitions in DA neurons and often ended several tens of milliseconds before the inhibitions began, making a causal relationship between these events unlikely. The inhibitions in Type III responses, combined with the inhibitions which followed the early excitations in many Type I and II responses, showed temporal characteristics that suggested a possible causal relationship with the excitations in DA neurons exhibiting E responses, but not those exhibiting IE responses. However, since the excitatory phases of E and IE responses appear to be homologous, the lack of involvement of non-DA neurons in the excitatory phase of IE responses tends to cast doubt on the involvement of non-DA neurons in the excitation during E responses. In fact, the most coherent impression that emerges is that non-DA neurons in the VTA do not influence the activity of A10 DA neurons on a short time-scale (i.e. phasically), but instead may influence activity on a longer time-scale (i.e. tonically).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050303
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  • 205
    Electronic Resource
    Electronic Resource
    Comparison of sympathetic sprouting in sensory ganglia in three animal models of neuropathic pain (1998)
    Springer
    Experimental brain research 120 (1998), S. 432-438 
    Details
    ISSN: 1432-1106
    Keywords: Key words Causalgia ; Hyperalgesia ; Mechanical allodynia ; Peripheral nerve injury ; Sympathetically maintained pain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sympathetic postganglionic fibers sprout in the dorsal root ganglion (DRG) after peripheral nerve injury. Therefore, one possible contributing factor of sympathetic dependency of neuropathic pain is the extent of sympathetic sprouting in the DRG after peripheral nerve injury. The present study compared the extent of sympathetic sprouting in the DRG as well as in the injured peripheral nerve in three rat neuropathic pain models: (1) the chronic constriction injury model (CCI); (2) the partial sciatic nerve ligation injury model (PSI); and (3) the segmental spinal nerve ligation injury model (SSI). All three methods of peripheral nerve injury produced behavioral signs of ongoing and evoked pain with some differences in the magnitude of each pain component. The density of sympathetic fibers in the DRG was significantly higher at all examined postoperative times than controls in the SSI model, while it was somewhat higher than controls only at the last examined postoperative time (20 weeks) in the CCI and PSI models. Therefore, data suggest that, although sympathetic changes in the DRG may contribute to neuropathic pain syndromes in the SSI model, other mechanisms seem to be more important in the CCI and PSI models at early times following peripheral nerve injury.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050416
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  • 206
    Electronic Resource
    Electronic Resource
    Influence of hypoglycemic coma on brain water and osmolality (1998)
    Springer
    Experimental brain research 120 (1998), S. 461-469 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypoglycemic coma ; Specific gravity ; Brain edema ; Tissue osmolality ; Blood-brain barrier permeability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the effects of pronounced hypoglycemia on brain osmolality and brain edema formation, fasted rats were rendered hypoglycemic by injection of insulin, and subjected to 30 min of hypoglycemic coma. Recovery was accomplished by glucose administration. The change in water content in different brain regions was measured as a change in specific gravity after 30 min of hypoglycemic coma, or 30, 60, and 180 min after glucose administration. Plasma and brain tissue osmolality were measured in separate animals. The results show a significant decrease in specific gravity (increase in water content) in all structures measured (caudoputamen, neocortex, hippocampus, and cerebellum) at the end of the period of coma, as well as after 30 min and 60 min of recovery. At 180 min of recovery, brain water was normalized. The edema affected all structures to the same degree regardless of their vulnerability to hypoglycemic damage. Brain tissue osmolality showed a tendency to decrease with decreasing tissue glucose content. The decrease was significant (P〈0.01) at 30 min of isoelectric coma. In the recovery phase, normal brain osmolality was restored within 30 min. Measurements of blood-brain barrier (BBB) permeability after 30 min of hypoglycemic coma showed no extravasation of Evan’s blue, though a small but significant increase in the permeability for aminoisobutyric acid (AIB) in caudoputamen and in cerebellum was found. To analyze the importance of tissue acidosis for formation of edema, hypoglycemic animals were made acidotic by increasing the CO2 concentration in inspired air to produce an arterial plasma pH of 6.8–6.9. In these animals the edema was of a similar degree to the normocapnic animals, and the permeability for AIB was normal. We conclude that osmolytic mechanisms are not the primary cause of the selective neuronal vulnerability in hypoglycemic coma. Furthermore, the BBB is largely intact during a hypoglycemic insult.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050419
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  • 207
    Electronic Resource
    Electronic Resource
    Calcium metabolism of focal and penumbral tissues in rats subjected to transient middle cerebral artery occlusion (1998)
    Springer
    Experimental brain research 120 (1998), S. 503-509 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular calcium concentration ; Total tissue calcium content ; Middle cerebral artery occlusion ; Reperfusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present experiments were undertaken to define changes in tissue calcium metabolism in focal and perifocal (“penumbral”) tissues following 2 h of transient middle cerebral artery occlusion (MCAO) in rats, induced with an intraluminal filament occlusion technique. The extracellular calcium concentration ([Ca2+]e) was measured with ion-selective microelectrodes in neocortical focus and penumbra. For measurement of total tissue calcium content, tissue samples from these areas were collected and analyzed with atomic absorption spectrometry. During MCAO, [Ca2+]e in a neocortical focal area fell from a normal value of about 1.2 mM to values around 0.1 mM, suggesting translocation of virtually all extracellular calcium to intracellular fluids. Recirculation was accompanied by re-extrusion of calcium within 5–7 min; however, [Ca2+]e never returned to normal but stabilized at about 50% of the control value for the first 6 h, and decreased further after 24 h. In penumbral areas, [Ca2+]e showed the expected transient decreases associated with spreading depression-like (or ischemic) depolarization waves. Recirculation was followed by return of [Ca2+]e towards normal values. In the focus, water content increased from about 79% to about 80.4% at the end of the 2-h period of ischemia. After 2 h and 4 h of recirculation, the edema was aggravated (mean values 81.9% and 81.2%, respectively). After 6 h and 24 h, the edema was more pronounced (83.6% and 83.8%, respectively). In the penumbra, no significant edema was observed until 6 h and 24 h of recirculation. The total tissue calcium content in the focus (expressed by unit dry weight) increased at the end of the ischemia period demonstrating calcium translocation from blood to tissue. After 6 h and 24 h, the content increased two- to threefold, compared with control. Changes in the penumbra were qualitatively similar but less pronounced, and a significant increase was not observed until after 6 h of recirculation. The results suggest that 2 h of MCAO leads to a profound perturbation of cell calcium metabolism. In focal areas, cells fail to extrude the calcium that is gradually accumulated during reperfusion and show massive calcium overload after the first 4–6 h of recirculation. Penumbral tissues show a similar increase in calcium concentration after 6 h of recirculation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050424
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  • 208
    Electronic Resource
    Electronic Resource
    Calbindin D28K and parvalbumin gene expression in rat embryonic ventral forebrain grafts (1998)
    Springer
    Experimental brain research 118 (1998), S. 551-563 
    Details
    ISSN: 1432-1106
    Keywords: Key words: Transplantation ; Calbindin D28K ; Parvalbumin ; Septum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study characterizes expression of calbindin D28 K (CB-D28 K) and parvalbumin (PV) in ventral forebrain (VFB) grafts placed in the neocortex of adult rats bearing quisqualic acid lesions to the nucleus basalis magnocellularis. Three to nine months after transplantation surgery, rats were killed for in situ hybridization with probes to CB-D28K or PV and for immunohistochemistry with antibodies to CB-D28K or PV. In addition, an antibody to choline acetyltransferase (ChAT) was used to characterize the cholinergic component in the graft and an antibody to tyrosine hydroxylase (TH) to explore catecholaminergic innervation of the graft. Quantitative analysis of CB-D28K and PV messenger ribonucleic acid (mRNA) was based on counts of silver grains generated by emulsion autoradiography. Cells expressing CB-D28K mRNA were significantly larger than such cells in the adult VFB and the mean number of silver grains per cell was significantly greater than to such cells in the adult VFB. The level of CB-D28K mRNA expression as calculated by ratio of silver grains per unit area was also significantly increased. Quantification of PV mRNA showed no significant differences between the cells in the graft and in the adult VFB. In order to begin to interpret these findings, a comparison was made with such cells in the VFB of developing rats. Brain sections were sampled from embryonic day 17 and postnatal days 1, 5, 12, 19 and adult (6–12 months of age). Cells expressing CB-D28K mRNA were detected in ventral forebrain from postnatal day 5 and cells expressing PV mRNA were detected in ventral forebrain from postnatal day 19. In the course of normal development of the ventral forebrain, no CB-D28K cells were found that were as large or expressed such high levels of CB-D28K mRNA as observed in the grafts. We conclude that changes in grafted cells expressing CB-D28K do not reflect an arrest of developmental processes. TH immunohistochemistry revealed lack of catecholaminergic innervation of the graft, whereas adult mediolateral septal cells that express CB-D28K receive such innervation in addition to other neurotransmitter inputs. Imbalance in neurotransmitter inputs to grafted cells expressing CB-D28K is discussed as a possible factor in their increased size and gene expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050311
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  • 209
    Electronic Resource
    Electronic Resource
    Modulation of mRNA expression of the neurotrophins of the nerve growth factor family and their receptors in the septum and hippocampus of rats after transient postnatal thyroxine treatment I. Expression of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin 4 mRNA (1998)
    Springer
    Experimental brain research 119 (1998), S. 1-8 
    Details
    ISSN: 1432-1106
    Keywords: Key words Thyroid hormone ; Neurotrophins ; Septum ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Early postnatal application of thyroid hormones to rats results in morphological changes in septum and hippocampus. Modulation in the expression of either neurotrophins and/or their receptors is postulated to be responsible for these effects. In the present study we tested whether thyroxine administration leads to changes in the expression of neurotrophins of the nerve growth factor (NGF) family. Newborn rats were treated daily with subcutaneous injections of thyroxine until postnatal day (P) 12 at maximum. The pups were killed at defined intervals from P2 to 21. The septal area and the hippocampi were analyzed using the reverse transcriptase-PCR method for quantitation of NGF, brain-derived neurotrophic factor (BDNF), NT-3, and NT-4 messenger RNA (mRNA) levels. In hippocampus of hyperthyroid rats, as compared to controls, we found higher levels of BDNF and NT-3 mRNA over the total investigation period, whereas in the septum a thyroxine-dependent increase in NT-3 mRNA expression was observed. In addition, significant thyroxine-induced effects were found for all variables (except for NGF in the septum) at particular postnatal days. From these data we conclude that modulation of neurotrophin expression is a possible mechanism for the morphological modifications within the hippocampal mossy fiber system and the septohippocampal cholinergic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050313
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  • 210
    Electronic Resource
    Electronic Resource
    Activation of the ornithine decarboxylase-polyamine system and induction of c-fos and p53 expression in relation to excitotoxic neuronal apoptosis in normal and microencephalic rats (1998)
    Springer
    Experimental brain research 120 (1998), S. 519-526 
    Details
    ISSN: 1432-1106
    Keywords: Key words Oncogene expression ; Polyamines ; Neuropathology ; Apoptosis ; Olfactory cortex ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Microencephalic rats obtained by gestational treatment with the DNA alkylating agent methylazoxymethanol, show a remarkable lack of sensitivity to excitotoxic neuropathology caused by systemic injections of the convulsant neurotoxin kainic acid. Taking advantage of this, we have studied in these rats, as well as in normal rats, the relationship between the induction of cellular signals supposedly related to cell death and the neuronal apoptosis consequent to kainic acid administration. While normal rats responded to the excitatory insult with a large and relatively long lasting increase of the activity of the enzyme ornithine decarboxylase and of the concentration of putrescine in some brain regions, these alterations were much smaller in microencephalic rats. Expression of c-fos in brain regions sensitive to kainic acid was quicker but lasted a noticeably shorter time in microencephalic rats as compared to normal animals. A profusion of apoptotic neurons, labeled by an in situ technique, were observed in the olfactory cortex, amygdala and hippocampus of normal rats injected with kainic acid, in particular 48 h and 72 h after drug administration. At corresponding time intervals and with similar topographic localization, neurons expressing p53 protein were observed. By contrast, microencephalic rats displayed only in a few cases and in a small number apoptotic neurons in restricted areas of the ventral hippocampus and entorhinal cortex. Noticeably, in these cases small populations of p53-expressing neurons were also present in the same areas. The present observations clearly show that oncogenes such as c-fos and p53, as well as ornithine decarboxylase which behaves as an immediate-early gene in the brain under certain circumstances, undergo noticeably lower and/or shorter induction in microencephalic rats exposed to excitotoxic stimuli. In these rats, therefore, the cellular signalling pathways studied here and related to excitotoxic sensitivity and committment to cell death are downregulated as a probable consequence of altered brain wiring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050426
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  • 211
    Electronic Resource
    Electronic Resource
    Posttraining epinephrine and memory consolidation in rats with different basic learning capacities The role of the stria terminalis (1998)
    Springer
    Experimental brain research 121 (1998), S. 20-28 
    Details
    ISSN: 1432-1106
    Keywords: Key words Stria terminalis ; Epinephrine ; Memory consolidation ; Two-way active avoidance ; Basic learning capacities ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats received bilateral stria terminalis (ST) lesions or were sham-operated. Five days later, the animals were trained in a two-way active avoidance task (one session, 30 trials) and, immediately after the training session, received 0.01 mg/kg i.p. epinephrine or distilled water. Retention was tested 20 days after the acquisition session. In sham-operated groups, epinephrine improved retention in rats that were poor learners and impaired it in rats that were good learners. In poor learners with posttraining epinephrine, lesions of the ST not only blocked the facilitatory effect of epinephrine but also disrupted performance throughout the retention session. In good learners, ST lesions attenuated the disruptive effect of epinephrine. Lesions per se did not affect either acquisition or retention. We conclude that ST is involved in the modulatory effect of posttraining epinephrine on memory consolidation. In addition and considering the results observed in rats that were poor learners, we suggest that emotional factors and/or other amygdaloid pathways different from the ST could participate in the effects of posttraining epinephrine, along with the ST.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050432
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  • 212
    Electronic Resource
    Electronic Resource
    Monotherapy with dextromethorphan or tirilazad – but not a combination of both – improves outcome after transient focal cerebral ischemia in rats (1998)
    Springer
    Experimental brain research 122 (1998), S. 121-127 
    Details
    ISSN: 1432-1106
    Keywords: Key words Dextromethorphan ; Tirilazad mesylate ; Combination drug therapy ; Cerebral ischemia ; Cerebral blood flow ; Neuroprotection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Cell death after cerebral ischemia is mediated by a massive release of excitatory amino acids, generation of free radicals, and – a crucial step – calcium influx into cells. We examined the hypothesis that concurrent administration of drugs ameliorating brain damage via different mechanisms would result in a synergistic neuroprotective effect. The neuroprotective efficacy of two clinically available drugs – the N-methyl-d-aspartate and calcium-channel antagonist dextromethorphan (DM) and the antioxidant tirilazad – were studied in monotherapy and in combination in a rat model of transient focal ischemia. Male Sprague-Dawley rats were subjected to 90 min of middle-cerebral-artery occlusion by an intraluminal filament technique. The animals were randomly assigned to one of four treatments (n=10 each): (1) vehicle-treated controls, (2) DM, (3) tirilazad, (4) DM+tirilazad. Drugs or vehicles were administered 15 min before ischemia and at reperfusion. Local cerebral blood flow (LCBF) was bilaterally recorded by continuous laser Doppler flowmetry. Functional deficits were quantified by daily neurological examinations. Infarct volume was assessed planimetrically after 7 days. DM prevented post-ischemic hypoperfusion. Tirilazad did not influence LCBF. Monotherapy with DM or tirilazad improved neurological function and reduced infarct volume by 45% and 48%, respectively. Combination therapy failed to influence neurological recovery and infarct volume. Although, from pharmacological point of view, a synergistic neuroprotective effect is expected, combination of dextromethorphan and tirilazad may lead to mutual inhibition or potentiate adverse effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050498
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  • 213
    Electronic Resource
    Electronic Resource
    Opioid inhibition of rat medial vestibular nucleus neurones in vitro and its dependence on age (1998)
    Springer
    Experimental brain research 122 (1998), S. 196-202 
    Details
    ISSN: 1432-1106
    Keywords: Key words Opioid ; Enkephalin ; Medial vestibular nucleus ; Age ; In vitro ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Extracellular and whole-cell patch clamp intracellular recordings were made from rat medial vestibular nucleus (MVN) neurones in vitro, and their responses to selective μ-, κ- and δ-opioid receptor agonists and antagonists were examined. Of 127 neurones tested, the large majority were inhibited in a dose-dependent manner by the δ-opioid receptor agonists [d-Ala2, d-Leu5]-enkephalin (DADLE) and [d-Pen2, Pen5]-enkephalin (DPLPE). The μ-opioid receptor agonist morphine and the κ-receptor agonist U50,488 did not affect the tonic discharge rate of any of the 63 MVN cells tested. The δ-receptor antagonist naltrindole effectively antagonised the inhibitory effects of DADLE and DPLPE. Weak excitatory responses to high doses of DADLE were seen in only two MVN cells. These results demonstrate the presence of δ- but not μ- or κ-opioid receptors on tonically active MVN neurones. Whole-cell intracellular recordings from MVN cells in a current clamp showed that the DADLE-induced inhibition was accompanied by membrane hyperpolarisation and decrease in input resistance, while voltage clamp experiments showed that DADLE induced an outward membrane current that was reduced but not abolished by 20 mM tetraethylammonium bromide. Thus the mechanisms of action of DADLE in inhibiting MVN cells involve the potentiation of outward K currents, in a similar way to the effects of opioids in other areas of brain. The inhibitory effects of DADLE increased linearly with age, so that the responses to DADLE in the youngest animals used here (60–80 g, approx. 3 weeks of age) were relatively small, increasing significantly over the following 2–3 weeks. This age-dependence may be due to post-natal changes in the density of δ-opiate receptors or the efficacy of the signalling pathways activated by them in the MVN cells over this time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050507
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  • 214
    Electronic Resource
    Electronic Resource
    Evidence that spinal endogenous opioidergic systems control the expression of chronic pain-related behaviors in spinally injured rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 259-268 
    Details
    ISSN: 1432-1106
    Keywords: Key words Central pain ; Endogenous opioids ; Naloxone ; Neuropathic pain ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and nonallodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of μ and δ opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective κ-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal κ-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal μ and δ, but not κ, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal pain-related behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050280
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  • 215
    Electronic Resource
    Electronic Resource
    On the cutaneous receptors contributing to withdrawal reflex pathways in the decerebrate spinal rat (1998)
    Springer
    Experimental brain research 118 (1998), S. 71-77 
    Details
    ISSN: 1432-1106
    Keywords: Key words Pain ; Nociception ; Analgesia ; Flexion reflex ; Spinal cord ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous studies indicate that the withdrawal reflex system in the rat has a “modular” organization, each reflex pathway performing a specific sensorimotor transformation. Here, we wished to clarify which cutaneous receptors contribute to this system and to determine whether there are differences in this respect between reflex pathways of different muscles. Withdrawal reflexes of the peroneus longus, extensor digitorum longus, and semitendinosus muscles were recorded with EMG techniques during high reflex excitability in decerebrate spinal rats (n=26). While maintained innocuous pressure on glabrous skin could elicit a sustained reflex activity in all muscles studied, vibration of glabrous skin (10–300 Hz) always failed to evoke a reflex response, suggesting that slowly adapting, but not rapidly adapting, low-threshold mechanoreceptive fibers from this type of skin contribute to withdrawal reflex pathways. Thermal stimulation in the innocuous range, i.e., cooling from 32 to 17°C, or warming the skin from 32 to 41°C, always failed to produce reflex responses, indicating that neither cold nor warm receptors contribute to withdrawal reflex pathways. When either cooling or warming the skin to the noxious temperatures of 1°C or above 45°C, respectively, a reflex discharge was often evoked in the muscles studied. Intradermal administration of histamine, a potent pruritogenic substance, produced very weak, or no, reflex response. In contrast, mustard oil produced vigorous reflex responses in all muscles studied. These findings suggest that some chemonociceptors contribute only weakly, or not at all, to withdrawal reflex pathways. The present data suggest that a selective set of cutaneous receptors contribute to withdrawal reflex pathways and that different withdrawal reflex pathways receive input from essentially the same cutaneous receptor types.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050256
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    Depletion of calcitonin gene-related peptide from the caudal trigeminal nucleus of the rat after electrical stimulation of the Gasserian ganglion (1998)
    Springer
    Experimental brain research 118 (1998), S. 111-114 
    Details
    ISSN: 1432-1106
    Keywords: Key words Caudal trigeminal nucleus ; Calcitonin generelated peptide ; Migraine ; Trigeminal ganglion ; Electrical stimulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electrical stimulation of the Gasserian ganglion resulted in partial depletion of calcitonin gene-related peptide (CGRP) from ipsilateral central terminals of pseudounipolar primary sensory ganglion cells. Affected terminals exhibit decreased CGRP immunoreactivity as shown by cytophotometric densitomery of the caudal trigeminal nucleus. The decrease in CGRP immunoreactivity is statistically significant only in the medial one-third of the caudal trigeminal nucleus. Since earlier studies have shown that electrical stimulation of the Gasserian ganglion induces first accumulation then depletion of CGRP from perivascular sensory terminals in the dura mater, the present experiments suggest that CGRP is depleted also from central terminals of primary sensory trigeminal neurons, which might be of importance in the pathogenesis of migraine headache.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050260
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    The corticostriatal system mediates the “paradoxical” contraversive rotation but not the striatal hyperexpression of Fos induced by amphetamine early after 6-hydroxydopamine lesion of the nigrostriatal pathway (1998)
    Springer
    Experimental brain research 120 (1998), S. 153-163 
    Details
    ISSN: 1432-1106
    Keywords: Key words Amphetamine ; Fos ; Rotational behavior ; Corticostriatal afferents ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In rats with unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway, amphetamine produces ipsiversive rotational behavior and activation of Fos in the intact striatum, but practically no activation of Fos in the denervated striatum. However, a seemingly paradoxical contraversive rotation, accompanied by intense striatal Fos activation in the lesioned striatum, has been observed during the first few days postlesion. In the present work, behavioral tests and immunohistochemistry for Fos protein and tyrosine hydroxylase (TH) were combined to study striatal changes 36 h after 6-OHDA lesion and particularly the possible involvement of glutamatergic corticostriatal afferents. Injection of amphetamine (0.5 mg/kg or 5 mg/kg) induced contraversive rotation and strong and evenly distributed Fos expression in the lesioned striatum; in the contralateral striatum, however, Fos density was lower than in nonlesioned rats. Pretreatment with the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (either 0.5 mg/kg or 5 mg/kg) did not significantly affect the hyperexpression of Fos in the lesioned striatum, but suppressed the contraversive rotation. Similarly, rats that were subjected to corticostriatal deafferentation (confirmed by sensory neglect tests) and 6-OHDA lesion (1 week or 3 weeks later) showed no significant reduction in the striatal Fos hyperexpression induced by amphetamine (0.5 mg/kg or 5 mg/kg) and no significant rotational asymmetry. In conclusion, the present results indicate that glutamatergic corticostriatal afferents are essential for the contraversive rotational behavior but not the striatal hyperexpression of Fos observed in response to amphetamine early after 6-OHDA lesion, and suggest that intense dopaminergic stimulation of striatal neurons is sufficient for induction of Fos, but that concurrent glutamatergic stimulation is necessary for the motor response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050389
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    Facilitation of learning after lesions of the tuberomammillary nucleus region in adult and aged rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 447-456 
    Details
    ISSN: 1432-1106
    Keywords: Key words Posterior hypothalamus ; Histamine ; Memory ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050301
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    Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter II. Evidence from selective inactivation of cell bodies and axon initial segments (1998)
    Springer
    Experimental brain research 118 (1998), S. 489-500 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Brain slice ; Intracortical microstimulation ; NMDA ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The results presented in the companion paper showed that extracellular electrical stimulation of the gray matter directly activates axons, but not cell bodies. The second set of experiments presented here was designed to separate the contribution of the axon initial segments and cell bodies from that of the axonal branches to the pool of presynaptic neuronal elements activated by electrical stimulation. For that purpose, N-methyl-d-aspartate (NMDA) iontophoresis was used to induce a selective inactivation of the cell body and of the adjoining portion of the axon by depolarization block, without affecting axonal branches that lack NMDA receptors. After NMDA iontophoresis, the neurons located near the iontophoresis electrode became unable to generate action potentials in an irreversible manner. When the NMDA-induced depolarization block was performed at the site of electrical stimulation, an unexpected increase in the amplitude of the orthodromic responses was observed. Several control experiments suggested that the field potential increase was due to changes of the local environment in the vicinity of the iontophoresis pipette, which led to an increased excitability of the axons. After the period of superexcitability, the orthodromic responses displayed an amplitude that was 15—20% lower than that observed before the NMDA-induced depolarization block, even though cell bodies and axon initial segment at the site of stimulation could not be activated by electrical stimulation. This result shows a low contribution for axon initial segments to the pool of neuronal elements activated by the electrical stimulation. Altogether, these experiments demonstrate that the postsynaptic responses obtained after electrical stimulation of the cortical gray matter result almost exclusively from the activation of axonal branches. Since the neocortex is organised as a network of local and long-range reciprocal connections, great attention must be paid to the interpretation of data obtained with electrical stimualtion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050305
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    Facilitatory effects of thalamic reticular nucleus lesions on two-way active avoidance in rats (1998)
    Springer
    Experimental brain research 118 (1998), S. 511-516 
    Details
    ISSN: 1432-1106
    Keywords: Key words Thalamic reticular nucleus ; Learning ; Memory ; Two-way active avoidance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Two experiments were performed in order to study the effects of lesions of the rostral thalamic reticular nucleus (Rt) on two-way active avoidance. Male wistar rats were subjected to either a bilateral electrolytical lesion of the rostral Rt or to control procedures. After recovery, all rats were trained in either a distributed (five training sessions, ten trials each; experiment I) or a massed (a single 30-trials session; experiment II) two-way, active-avoidance task. The level of long-term retention of the task was assessed 10 days later. Lesioned rats showed an overall higher performance than control rats both in experiment I (with lesions affecting the rostral Rt and small portions of some adjacent nuclei) and in experiment II (with lesions almost restricted to the rostral Rt). In contrast, detrimental effects on other tasks have been reported in the literature. Although it cannot be ruled out that those differences might be due to methodological factors, they also might be indicative of an action of rostral Rt lesions on certain mechanisms (either indirectly or directly related to information processing) that could be differentially required depending on the kind of learning task. The latter possibility is discussed in terms of the role played by this nucleus as a modulator of thalamocortical transmission, attentional mechanisms and cortical arousal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050307
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    Comparison of the rat dorsal and ventral striatopallidal system A study using the GABAA-receptor α1-subunit and parvalbumin immunolabeling (1998)
    Springer
    Experimental brain research 121 (1998), S. 215-221 
    Details
    ISSN: 1432-1106
    Keywords: Key words GABAA-receptor α1-subunit ; Parvalbumin ; Striatum ; Pallidum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventral striatum is more closely related to limbic brain regions than the dorsal striatum in spite of the remarkable similarities in the structural organization between these two brain regions. The present study is focused on the comparison of ventral striatopallidal territories and the dorsal striatopallidal system regarding the GABAA-receptor α1-subunit and parvalbumin immunoreactivity, as these markers showed specific distribution patterns and coexpression sites in the more intensely studied dorsal regions. Our investigations revealed that: (1) Parvalbumin single-labeled cells and a moderate number of neurons single-labeled with the GABAA-receptor α1-subunit exist not only in the dorsal but also in the ventral striatum, including the striatal cell bridges. In addition, morphologically similar neurons positive for the α1-subunit were also found in the corpus callosum and anterior commissure. (2) A small number of double-labeled neurons was seen not only in dorsal but also in ventral striatal regions. Such cells were mainly located near the border with the globus pallidus and ventral pallidum. They are likely to represent a further type of striatal neuron. (3) The vast majority of neurons in the entopeduncular nucleus, the homologue of the primate internal globus pallidus segment, coexpressed α1-subunit and parvalbumin immunoreactivity, as reported previously for the other pallidal compartments. (4) The islands of Calleja adjoining the ventral pallidal extensions in the olfactory tubercle exhibited a strong α1-subunit immunoreactivity in the neuropil as well as somata single- or double-labeled for both markers. Our findings indicate that the dorsal and ventral striatopallidal compartments are similarly organized in general with respect to the occurrence and distribution of single- and double-labeled parvalbumin-immunoreactive and GABAA-receptor α1-subunit-immunoreactive neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050454
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    Bötzinger-complex expiratory neurons monosynaptically inhibit phrenic motoneurons in the decerebrate rat (1998)
    Springer
    Experimental brain research 122 (1998), S. 149-156 
    Details
    ISSN: 1432-1106
    Keywords: Key words Respiration ; Bötzinger complex ; Phrenic motoneurons ; Bulbospinal expiratory neurons ; Intracellular recording ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We examined respiratory neurons in the Bötzinger complex of the medulla oblongata in 18 vagotomized, paralyzed, ventilated, and decerebrated rats and tested the hypothesis that bulbospinal expiratory neurons in this region monosynaptically inhibit phrenic motoneurons. First, we surveyed the types of respiratory neurons found in the Bötzinger complex; only 11 of the 98 (∼11%) examined were bulbospinal, and all discharged only during late expiration (E2), usually with an augmenting discharge frequency (AUG). Then, we examined the spinal projections of 34 E2-AUG neurons using antidromic activation and found that all projected as far as the C4 or C5 segments of the spinal cord but no further caudally. Most (30, ∼88%) had only unilateral projections, the majority (25, ∼83%) ipsilateral, but 4 neurons (∼12%) had bilateral projections. Their axons could be antidromically activated at low currents (less than 10 μA) in the dorsal-lateral part of the spinal cord at the C2–3 border; 0.5–1.2 mm (mean±SD 0.84±0.23 mm) below the dorsal surface and 0.7–1.5 mm (1.19±0.25 mm) lateral from the midline. We sought evidence for connections from bulbospinal E2-AUG neurons to 118 phrenic motoneurons by computing spike-triggered averages (STAs) of their intracellular potentials triggered by the action potentials of 38 unilaterally-projecting E2-AUG neurons. Resting phrenic motoneuron membrane potentials ranged from –40 to –75 mV (–56±8 mV) and fluctuations with the respiratory cycle from 7 to 20 mV (14±4 mV). Of the 118 STAs computed, hyperpolarizations were evident in 18 (∼15%) STAs, evoked by 11 of 38 (∼29%) E2-AUG neurons. Their amplitudes varied from 35 to 550 μV (105±113 μV), 10–90% fall times from 0.4 to 0.9 ms (0.63±0.17 ms), and half-amplitude widths from 1.3 to 3.2 ms (2.0±0.52 ms). Most (16/95, ∼17%) of the STAs that displayed hyperpolarizations were associated with ipsilateral trigger neurons but some (2/23, ∼9%) resulted from contralateral trigger neurons. We conclude that Bötzinger-complex, expiratory neurons project to the C4 and/or C5 segments of the cervical spinal cord but no further caudal. Their axons are located dorsolaterally in the upper cervical segments of the spinal cord, and they monosynaptically inhibit phrenic motoneurons during the late part of expiration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050502
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    Cyclophosphamide cystitis as a model of visceral pain in rats: a c-fos and Krox-24 study at telencephalic levels, with a note on pituitary adenylate cyclase activating polypeptide (PACAP) (1998)
    Springer
    Experimental brain research 122 (1998), S. 165-174 
    Details
    ISSN: 1432-1106
    Keywords: Key words Urinary bladder ; Inflammation ; Nucleus centralis of amygdala ; Bed nucleus of the stria terminalis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This article is the fifth of a series aimed at mapping brain activities as they result from the development of cyclophosphamide (CP) cystitis in behaving rats using c-fos and Krox-24 expression. The inactive hepatic metabolites of CP are metabolized in the kidney to produce acrolein, which generates cystitis. Data come from animals which were injected once i.p. with either 1 ml saline (sham) or 100 mg/kg CP in 1 ml saline under transient volatile anesthesia and which behaved freely for 1–4 h postinjection, 4 h being the minimum time for cystitis to completely develop. Survival times longer than 4 h were not studied owing to ethical considerations. The first 2 h postinjection cover a period of time over which inputs of multifactorial origin (stress and pain due to the intraperitoneal injection process, possible effects due to the presence of hepatic CP metabolites in blood, cystitis onset) interact in an indistinguishable way; the last 2 h are more cystitis specific as the other effects have vanished. Complete screening of telencephalic levels has been performed. These data complete previously published data at both spinal and subtelencephalic levels. Of all the telencephalic structures, only the bed nucleus of the stria terminalis in the dorsal part of its lateral division (BSTLd) and, to a lesser degree, the nucleus centralis of the amygdala, mostly in its caudal portion (cCeA), appeared to be significantly driven over the most specific cystitis period. Both of these structures had related, but not identical patterns of expression. They both reacted shortly after CP injection, but, while cCeA maintained its activity throughout cystitis development, BSTLd showed a rebound, reaching a peak value when cystitis was fully developed. Both of these areas are the only telencephalic areas to contain high PACAP38 immunoreactivity. This is evidence that, (1) both the BSTLd and cCeA could be the most rostral areas that visceronociceptive inflow would reach when cystitis genesis is under way, and (2) PACAP38 could be one of the neurochemical agents involved in telencephalic visceronociceptive processing. From our complete mapping of brain activities under a fully developed cystitis situation (4 h postinjection), it appears that the activities in BSTLd and cCeA are concomittant with those of both the dorsal vagal complex (DVC), paratrigeminal nucleus (PaT), and the ventrocaudal bulbar reticular formation (vcBRF) at brainstem levels, suggesting they all form the main part of the neural network that subserves the central processing of cystitis-related inputs, comprising pain and associated pseudoaffective responses. Both the DVC and BSTLd, which are the most powerfully driven areas, would be particularly important in such a way. The origin of these activities should be found in both vagal (as sensed through PaT activity) and spinal (pelvic) influences. This network profoundly differs from those reported for painful situations, either somatic or visceral, which controversally accompany positive cardiac inotropism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050504
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    Hypothermia attenuates hyperglycolysis in the periphery of ischemic core in rat brain (1998)
    Springer
    Experimental brain research 122 (1998), S. 333-338 
    Details
    ISSN: 1432-1106
    Keywords: Key words Hypothermia ; Cerebral ischemia ; Glucose metabolism ; Middle cerebral artery occlusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Hypothermia has proven to be neuroprotective against ischemic brain injury. However, the exact mechanism has not yet been fully understood. In this study, we investigated the effects of hypothermia on cerebral glucose metabolism and blood flow in focal ischemic rats. Rats were divided into normothermic (37±0.5°C) and hypothermic (30±0.5°C) groups. Focal cerebral ischemia was induced by middle cerebral and ipsilateral common carotid arteries occlusion. Two hours after ischemia, autoradiographic studies of 2-deoxyglucose and iodoantipyrine were performed to measure local cerebral glucose utilization (LCGU) and cerebral blood flow. LCGU in the ischemic core was excessively reduced in both groups. However, a marked increase in LCGU was observed in the boundary zone of the ischemic core in normothermic rats. On the other hand, hyperglycolysis in the boundary zone of the ischemic core was suppressed in hypothermia. This attenuation of hyperglycolysis might be closely related to survival of the ischemic penumbra in hypothermia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050521
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    Anxiolytic-like behavior after lesion of the tuberomammillary nucleus E2-region (1998)
    Springer
    Experimental brain research 119 (1998), S. 260-264 
    Details
    ISSN: 1432-1106
    Keywords: Key words Tuberomammillary nucleus ; Ibotenic acid ; Fear and Anxiety ; Elevated plus-maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, consists of five subgroups and is the only known source of brain histamine. In the present experiment, rats received bilateral ibotenic acid or sham lesions in the rostroventral part of the TM (E2-region). Three weeks later they were tested on the elevated plus-maze test of fear and anxiety. Lesions in the tuberomammillary E2-region elevated the time spent on the open arms, as well as excursions into the end of the open arms, increased scanning over the edge of an open arm, and decreased risk-assessment from an enclosed arm. Thus, partial destruction of TM intrinsic neurons can induce anxiolytic-like effects which are possibly related to a lesion-induced reduction of histaminergic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050340
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    Intranigral ventral mesencephalic grafts and nigrostriatal injections of glial cell line-derived neurotrophic factor restore dopamine release in the striatum of 6-hydroxydopamine-lesioned rats (1998)
    Springer
    Experimental brain research 119 (1998), S. 287-296 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glial cell line-derived neurotrophic factor ; Dopamine ; Parkinson’s disease ; Substantia nigra grafts ; Voltammetry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that grafting of fetal ventral mesencephalic (VM) tissue to the nigral region of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats, in conjunction with glial cell line-derived neurotrophic factor (GDNF) injection between nigra and striatum, restores nigrostriatal tyrosine hydroxylase (TH) immunoreactivity. In this study, we investigated the electrochemical indices of dopamine (DA) release in these grafted animals in the striatum and nigra. Adult Sprague-Dawley rats were anesthetized and unilaterally injected with 6-OHDA into the medial forebrain bundle. The completeness of lesions was tested by measuring methamphetamine-induced rotations. One to two months after 6-OHDA administration, fetal VM tissues were grafted in the lesioned nigral area followed by injection of GDNF, brain-derived neurotrophic factor (BDNF), or phosphate-buffered saline (PBS), along a tract from nigra to striatum. Animals receiving transplantation and GDNF, but not BDNF or PBS, injection showed a significant decrease in rotation 1–3 months after grafting. High-speed chronoamperometric recording techniques, using Nafion-coated carbon fiber electrodes, were used to evaluate DA overflow in the striatum. We found that 6-OHDA lesions resulted in a loss of KCl-induced DA overflow in the urethane-anesthetized rats. Three months after GDNF-bridged grafting, application of KCl elicited DA release both in nigra and striatum. The KCl-evoked DA release area was limited to the GDNF-bridging tract in the striatum. On the other hand, KCl did not induce DA release in the BDNF- or PBS-bridged grafts. Immunocytochemical studies indicated that TH-positive neurons and fibers were found in the nigra and striatum after GDNF-bridged grafting. Taken together, our data suggest that fetal nigral transplantation and GDNF injection may restore the nigrostriatal DA pathway and DA release in these hemiparkinsonian animals and support the hypothesis of trophic activity of GDNF on fiber outgrowth from midbrain DA neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050344
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    Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 345-355 
    Details
    ISSN: 1432-1106
    Keywords: Key words Neural transplantation ; Tyrosine hydroxylase ; Calcium-binding proteins ; Parkinson’s disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 ± 98, mean ± SEM) and grafts of fresh, dissociated cell suspension (806 ± 105, mean ± SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050350
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    Correlation of electrophysiology, morphology, and functions in corticotectal and corticopretectal projection neurons in rat visual cortex (1998)
    Springer
    Experimental brain research 119 (1998), S. 375-390 
    Details
    ISSN: 1432-1106
    Keywords: Key words Visual cortex ; Superior colliculus ; Nucleus of the optic tract ; Electrophysiology ; Morphology ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In most mammals the superior colliculus (SC) and the pretectal nucleus of the optic tract (NOT) receive direct input from the ipsilateral visual cortex via projection neurons from infragranular layer V. We examined whether these projection neurons belong to different populations and, if so, whether it is possible to correlate the electrophysiological features with the suggested function of these neurons. Projection cells were retrogradely labeled in vivo by rhodamine-coupled latex beads or fast blue injections into the SC or the NOT 2–5 days prior to the electrophysiological experiment. Intracellular recordings of prelabeled neurons were made from standard slice preparations and cells were filled with biocytin in order to reveal their morphology. Both cell populations consist of layer V pyramids with long apical dendrites that form terminal tufts in layer I. In electrophysiological terms, 12 of the corticotectal cells could be classified as intrinsically bursting (IB), while two neurons showed a doublet firing characteristic and one neuron was classified as regular-spiking (RS). Intracortical microstimulation of cortical layer II/III revealed that SC-projecting neurons responded optimally to stimulation sites up to a distance of 1000 μm from the recorded cell. The morphological features of the SC-projecting cells reveal an apical dendritic tuft in layer I with a lateral extension of 300 μm, a mean spine density of 65 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 13 boutons per 100 μm on the intracortical axons. Sixteen NOT-projecting neurons exhibited an IB and five cells an RS characteristic. Intracortical microstimulation of cortical layer II/III showed that NOT-projecting neurons responded optimally to stimulation sites up to a distance of 1500 μm. Their morphological features consist of an apical dendritic tuft with a lateral extension of 500 μm, a mean spine density of 25 spines per 40 μm on the apical dendrites located in layer II/III, and a bouton density of 6 boutons per 100 μm on the intracortical axons. When the passive membrane parameters, responses to intracortical microstimulation in layer V, the extension of the basal dendritic field, and spine densities in layers I or V were compared between SC- and NOT-projecting cells, no differences were revealed. Differences were only consistently found in the supragranular layers, either for morphological parameters or for intracortical microstimulation. The results suggest that NOT-projecting and SC-projecting neurons, although biophysically similar, could integrate and transmit different spatial aspects of cortical visual information to their target structures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050353
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    The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task (1998)
    Springer
    Experimental brain research 119 (1998), S. 517-528 
    Details
    ISSN: 1432-1106
    Keywords: Key words Entorhinal cortex ; Medial septal nucleus ; Working memory ; T-maze ; Delayed matching-to-position ; Hippocampus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex (ECx) were compared postoperatively with unoperated controls in a discrete-trial, delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP trial consisted of two consecutive visits to the maze: an information run and a choice run. The animals were first forced to visit a randomly selected choice arm in the information run. In the choice run, the correct response was to match the choice arm that had been visited on the information run, regardless of whether the information run itself had been rewarded or not. MSN animals failed to succeed in this task, performing at close to chance level throughout training. On the other hand, ECx rats consistently perform at a level comparable with that of unoperated controls; both groups attained more than 90% correct after 192 trials. Long-term retention testing was carried out after an intermission of 4 weeks, when the same task was re-administered to the ECx and unoperated control animals. ECx animals showed significantly less saving than controls in the retention test. In contrast, when the retention interval within a DMTP trial was increased by the imposition of a 20-s delay between the information and choice runs, the ECx group was not selectively affected by this manipulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050368
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    Time course of changes in EMG activity of fast muscles after partial denervation (1998)
    Springer
    Experimental brain research 120 (1998), S. 193-201 
    Details
    ISSN: 1432-1106
    Keywords: Key words EMG ; Motor unit activity ; Partial denervation ; Interlimb coordination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  After partial denervation, the remaining motor units (MUs) of adult fast extensor digitorum longus muscle (EDL) expand their peripheral field. The time course of this event was studied using tension measurement and recordings of electromyographic (EMG) activity. The results show that after section of the L4 spinal nerve, when only 5.3 ± 0.63 of the 40 MUs normally supplying EDL muscle remain, the force of individual motor units starts to increase between the 1st and 2nd week after the operation and continues to do so for a further week. The drastic reduction of the number of motoneurones supplying the fast EDL leads to an increase in activity of the remaining MUs. In the 1st week after partial denervation, there was a sharp increase in the EMG activity of remaining motor units. During the next 12 days, this increase became less marked, but EMG activity remained nevertheless significantly higher than that of the unoperated EDL muscle. Many MUs became tonically active during posture. The EMG activity pattern during locomotion was also altered, so that the burst duration was positively correlated with the step cycle duration. Moreover, shortly after partial denervation, the interlimb coordination was disturbed but returned to its original symmetrical use 1–2 weeks later.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050393
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    Developmental changes in NMDA receptor-mediated visual activity in the rat superior colliculus, and the effect of dark rearing (1998)
    Springer
    Experimental brain research 120 (1998), S. 335-344 
    Details
    ISSN: 1432-1106
    Keywords: Key words Plasticity ; Glutamate ; AP5 ; Visual Deprivation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  N-methyl-D-aspartate (NMDA) receptor-mediated activity is considered important for experience-dependent plasticity in the developing visual system. We investigated the influence of age and experience on the role of NMDA receptors in the visual transmission in the superficial grey layer of the superior colliculus (SGS) of the superior colliculus, where, in the adult, NMDA receptors mediate a substantial part of the visual response. In normally reared (postnatal day 14, P14, to adult) rats, visual responses were challenged with NMDA receptor-selective iontophoretic applications of the antagonist D-2-amino-5-phosphonovalerate (AP5). After eye opening (at P14), there was a significant increase in the number of neurones whose visual responses were reduced during AP5 ejection, which peaked at P22 (85%; n = 21), and then declined to adult levels (66%; n = 47) at P25. The mean reduction of the response (from control levels) by AP5 was similar at all ages (approximately 40%). Dark rearing had striking effects on the role of NMDA receptors in visual transmission, especially when comparisons were made between age-matched subjects greater than P25. In these subjects, AP5 ejection reduced the visual responses of all neurones studied. In addition, AP5 ejection caused a significantly larger reduction of visual responses in dark-reared rats (mean reduction 62 ± 4; n = 29) compared with age-matched controls (mean reduction 44 ± 8; n = 23). The D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the visual responses of every neurone studied and there were no age- or experience-dependent effects. We conclude that NMDA receptors, but not AMPA receptors, assume greater importance for visual transmission in the SGS of dark-reared rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050407
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    Dual (excitatory and inhibitory) calretinin innervation of AMPA receptor-containing neurons in the rat lateral septum (1998)
    Springer
    Experimental brain research 119 (1998), S. 65-72 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glutamate receptor ; GABA ; Double immunostaining ; Colocalization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A recent study demonstrated both an extrinsic and an intrinsic calretinin (CR) innervation of the rat septal complex and that a population of the extrinsic calretinin fibers is aspartate/glutamate-containing. The aim of this study was to determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing lateral septal area neurons are innervated by extrinsic and intrinsic CR neurons and whether the intrinsic CR cells are GABAergic. Light- and electron-microscopic single immunostaining for CR, GluR1, and GluR2/3, as well as light- and electron-microscopic-double immunostaining experiments for CR plus GluR1 and CR plus GluR2/3 were performed in the lateral septal area. Furthermore, the ″mirror″ colocalization technique was employed on consecutive vibratome sections of the septal complex to investigate whether the intrinsic septal CR neurons are GABAergic. The results are summarized as follows: (1) both GluR1- and GluR2/3-immunoreactive neurons are innervated by CR-containing fibers; (2) the majority of these synapses, observed mainly on the soma and, to a lesser extent, on proximal dendrites of AMPA receptor-containing neurons, represent asymmetric synaptic membrane specializations; (3) a minority of CR-containing axon terminals associated with both GluR1- and GluR2/3-immunoreactive neurons form symmetric contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR cells are GABAergic. These observations indicate that both GluR1- and GluR2/3-containing lateral septal area neurons receive a dual intrinsic and extrinsic CR innervation. The former (intrinsic) CR boutons are GABAergic, while the latter form asymmetric synaptic contacts, are excitatory, and probably originate in the supramammillary area, since previous work has demonstrated that a population of supramammillo-septal fibers contain aspartate and/or glutamate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050320
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    Acute and long-lasting changes in extracellular-matrix chondroitin-sulphate proteoglycans induced by injection of chondroitinase ABC in the adult rat brain (1998)
    Springer
    Experimental brain research 121 (1998), S. 300-310 
    Details
    ISSN: 1432-1106
    Keywords: Key words Extracellular matrix ; Proteoglycans ; Chondroitinase ; Cerebral cortex ; Plasticity ; Regeneration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties (’stubs’) of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050463
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    Reaction of Müller cells after increased intraocular pressure in the rat retina (1998)
    Springer
    Experimental brain research 121 (1998), S. 419-424 
    Details
    ISSN: 1432-1106
    Keywords: Key words Glial fibrillary acidic protein ; Müller cell ; Increased intraocular pressure ; Retina ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Using light microscopy and immunocytochemistry, we investigated the morphological changes of retinal tissues and the reaction of Müller cells in the ischemic rat retina induced by increasing intraocular pressure. At early stages (from 1 h to 24 h after reperfusion), cells in the ganglion cell layer and in the inner nuclear layer showed some degenerative changes, but at later stages (from 72 h to 4 weeks) marked degenerative changes occurred in the outer nuclear layer (ONL). At 4 weeks after reperfusion, the ONL was reduced to 1 or 2 cell layers. Immunoreactivity for glial fibrillary acidic protein (GFAP) appeared in the endfeet and distal processes of Müller cells as of 1 h after reperfusion. GFAP immunoreactivity in Müller cells increased up to 2 weeks and then decreased at 4 weeks after reperfusion. Our findings suggest that Müller cells are involved in the pathophysiology of retinal ischemia through the expression of GFAP. The degree of GFAP expression in Müller cells closely correlated with that of the degeneration of retinal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050476
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    Renal excretory responses of taurine-depleted rats to hypotonic and hypertonic saline infusion (1998)
    Springer
    Amino acids 15 (1998), S. 109-116 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; Taurine ; Rat ; Natriuresis ; Hypotonic saline ; Hypertonic saline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Wistar-Kyoto rats were given either tap water (control) or 3%β-alanine (taurine-depleted) for three weeks. To prepare for the kidney function studies, the animals were then implanted with femoral vessels and bladder catheters. Two days after surgery, each rat was given an intravenous infusion of saline at the rate of 50μl/min and urine samples were collected at specific time intervals. An isotonic saline solution (0.9% NaCl) was infused for determination of baseline parameters and was followed by the infusion of a hypotonic saline solution (0.45% NaCl). Two days later, the infusion protocol was repeated in the same animals; however, a hypertonic saline solution (1.8% NaCl) was substituted for the hypotonic saline solution. Renal excretion of fluid and sodium increased in the control, but not taurine-depleted, rats during the hypotonic saline infusion. Interestingly, diuretic and natriuretic responses were similar between the groups during hypertonic saline infusion. The results suggest that taurine-depletion in rats affects renal excretory responses to a hypotonic, but not a hypertonic, saline solution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345284
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    Expression and localization of cysteine dioxygenase mRNA in the liver, lung, and kidney of the rat (1998)
    Springer
    Amino acids 15 (1998), S. 143-150 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; In situ hybridization ; Cysteine dioxygenase ; Liver ; Lung ; Kidney ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The expressions of cysteine dioxygenase (CDO) gene in the liver, lung, skeletal muscle, and kidney were studied byin situ hybridization with a cDNA probe from rat liver CDO under normal conditions. Significant expression of the CDO gene was detected in the liver, lung, and kidney, but not skeletal muscle. In the liver, the signal was confined to the cytoplasm of the hepatocytes. Furthermore, the signal was stronger in the periportal than that in the perivenous areas. In the lung, an intensive signal was found in the bronchiolar epithelium. As to the kidney, an intensive signal was observed in the distal convoluted tubules, while no signal was found in the proximal convultions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345287
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    Whole body autoradiographic study on the distribution of14C-d-serine administered intravenously to rats (1998)
    Springer
    Amino acids 15 (1998), S. 351-361 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; 14C-l-Serine ; Rat ; Whole body autoradiography ; Accumulation ; Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The distribution of radioactivities in rats following intravenous administration of14C-d- or -l-serine was investigated by whole body autoradiography. The radioactivities were distributed throughout the whole body in both cases with the greatest amount being found in the pancreas. D- andl- Serine levels in the pancreas were determined by high-performance liquid chromatography with a chiral column which revealed, for the first time, the existence ofd-serine in the rat pancreas (12.6 ± 7.90 nmol/g wet tissue) together with a much higher concentration (924 ± 116 nmol/g) ofl-serine. The results suggested that exogenous D-serine of dietary origin contributed at least in part to the D-serine levels found in mammalian tissues. The accumulation of radioactivity in the kidney, especially in the corticomedullary area, even at 24 hr after administration of14C-l-serine suggested a possible link between acute necrosis of the renal proximal tubules and the administration of a large dose of D-serine [Am J Pathol 77: 269–282 (1974)].
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01320899
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    Release of endogenous excitatory amino acids in the neostriatum of the rat under physiological and pharmacologically-induced conditions (1998)
    Springer
    Amino acids 14 (1998), S. 197-203 
    Details
    ISSN: 1438-2199
    Keywords: Basal ganglia ; Excitatory amino acids ; Monoamines ; Neuropeptides ; Microdialysis ; Immunocytochemistry ; Parkinson's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is immunohistochemical evidence suggesting that glutamate (Glu) is released from nerve terminals and acts, via several receptor subtypes, as a major excitatory neurotransmitter in the cortico-striatal pathway of the rat. Aspartate (Asp) is also present in cortico-striatal neurons, but its role as a neurotransmitter has been questioned, since, in contrast to Glu, it has not been demonstrated in presynaptic vesicles. Glu and Asp can be found at subμM concentrations in the extracellular compartment of most areas of the basal ganglia. Their concentrations are largely regulated by transport mechanisms, but also by a synaptotagmin-dependent exocytotic release, and are sufficiently high to occupy junctional and extrajunctional receptors. We have investigated whether Glu and Asp release in the neostriatum can be selectively modulated by different neuronal systems. Dopamine (DA) and cholecystokinin (CCK) selectively stimulate Asp release, via D1 and CCKB receptor subtypes, respectively. Also opioid κ-agonists increase Asp release. We propose that the selective modulation of Asp release by D1−, CCKB- and κ agonists involves striatal neurons containing Asp, but not Glu. In contrast, local perfusion with the ,μ-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-ThrPen-Thr-NH2 (CTOP) increases both Glu and Asp release. This effect is probably exerted on cortico-striatal terminals, via presynaptic inhibitory μ-receptors. Thus, these results demonstrate that extracellular levels of Glu and Asp are modulated differentially by different neuronal systems, and suggest that in the neostriatum of the rat there are neuronal populations using Glu and/or Asp as messenger(s).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345262
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    Fetal adrenal transplants respond to ACTH and prevent addisonian crisis in adrenalectomized rats (1998)
    Springer
    Pediatric surgery international 13 (1998), S. 271-273 
    Details
    ISSN: 1437-9813
    Keywords: Key words Fetal transplantation ; Adrenals ; Addisonian crises ; Rat ; Adrenocorticotropic hormone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study investigates whether fetal adrenal transplants into the omentum of adrenalectomized rats will be integrated into the recipient's endocrine system to provide competent adrenocortical function. The results demonstrate that fetal adrenals graft with a rich vascular supply, mature histologically, and produce increasing levels of corticosterone. When bilateral adrenalectomy is performed in the recipient, survival is prolonged and addisonian crisis can be prevented. Moreover, adrenocorticotrophic hormone levels decrease with increasing levels of corticosterone, indicating that the fetal grafts are integrated into the physiological pituitary-adrenocortical feedback system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003830050314
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    Locally infused taurine, GABA and homotaurine alter differently the striatal extracellular concentrations of dopamine and its metabolites in rats (1998)
    Springer
    Amino acids 15 (1998), S. 117-134 
    Details
    ISSN: 1438-2199
    Keywords: Amino acids ; Striatal dopamine release ; Intrastriatal taurine ; GABA ; Homotaurine ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studiedin vivo the effects of locally infused taurine (50, 150, and 450 mM) on the striatal dopamine and its metabolites in comparison with those of GABA and homotaurine, a GABAA receptor agonist, in freely moving rats. The extracellular dopamine concentration was elevated maximally 2.5-, 2- and 4-fold by taurine, GABA and homotaurine, respectively. At 150 mM concentration, at which the maximum effects occurred, homotaurine increased the extracellular dopamine more than taurine or GABA. When taurine and GABA were infused simultaneously with tetrodotoxin the output of dopamine did not differ from that in the presence of tetrodotoxin alone. In comparison, tetrodotoxin did not inhibit the increase in extracellular dopamine caused by homotaurine. Furthermore, omission of calcium from the perfusion fluid inhibited the increase of extracellular dopamine caused by GABA. However, it did not block the increase of dopamine caused by taurine or homotaurine. The present study suggests that the effects of intrastriatal taurine, GABA and homotaurine on the striatal extracellular dopamine differ. Thus, these amino acids seem to affect the striatal dopaminergic neurons via more than one mechanism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01345285
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    The difference of HSP72 induction in rat’s systemic organs after burn injury depends on burned body surface area (1998)
    Springer
    European journal of plastic surgery 21 (1998), S. 91-94 
    Details
    ISSN: 1435-0130
    Keywords: Key words Burn injury ; Stress protein ; Systemic organs ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously reported that in severely burned rats, the induction of 72-kD stress protein (HSP72) increased in various systemic organs. In this present study, in order to compare the stress response of systemic organs to burn injury of a smaller total body surface area with those of an extensive burn, we investigated the induction of 72-kD heat shock protein (HSP72) in various organs (brain, hypophysis, lung, heart, liver, pancreas, spleen, kidney, adrenal gland, and skeletal muscle) of burned rats. A dermal burn was developed on the skin by immersing the rats in hot water (90° C) for three seconds. At 0, 24 and 48 h after burn injury, the HSP72 induction of various organs was examined by Western blot analysis. In the single hind leg burn, the level of HSP72 did not increase at any time in all ten organs. In the double hind leg burn, at 48 h, the induction of HSP72 increased more than 1.5 fold compared to the control in the hypophysis (1.6 fold) and the heart (1.8 fold). These results indicate that the double hind leg burn causes a stress response in the hypophysis and the heart, while the single hind leg burn does not cause this stress response. In extensively burned rats, the degree of the stress response of the systemic organs to the burn injury depends on the burn size, and the intensity of “burn stress” to the systemic organs in a double or single hind leg burn is relatively small compared with those in extensive burns at the molecular level.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002380050034
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    Additive effect of concomitant multiple low-dose doxorubicin and thoracic irradiation on ex vivo cardiac performance of the rat heart (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 148-154 
    Details
    ISSN: 1432-1335
    Keywords: Key words Irradiation ; mld-doxorubicin ; Isolated working rat heart preparation ; Heart function ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of doxorubicin alone or combined with local heart irradiation on ex vivo cardiac performance were studied in Sprague-Dawley rats. Rats were treated with doxorubicin either administered as a single bolus injection or administered weekly during a period of 10 weeks. In “combined” experiments, local heart irradiation with a single dose of 15 Gy was given prior to drug administration. Evaluation of cardiac performance was performed 14 weeks after initiation of treatment. At drug doses that were tolerated by the rat, single injections with doxorubicin (sd-DXR; up to a dose of 5 mg/kg) did not lead to a change in cardiac performance whereas multiple injections with low-dose doxorubicin (mld-DXR; up to a cumulative dose of 20 mg/kg) led to a dose-dependent decrease in cardiac function. Extracardial toxicity as a result of mld-DXR (cumulative dose ≤15 mg/kg) was mild when compared to the toxicities observed after sd-DXR (5.0 and 7.5 mg/kg). When administration of mld-doxorubicin was preceded by 15 Gy, cardiac performance further decreased. The present data indicate that the interaction between doxorubicin and local heart irradiation with a dose of 15 Gy is additive, when the treatments are given concomitantly. Irradiation did not lead to an increase of DXR-mediated extracardial toxicities. The isolated working rat heart preparation offers a reliable method to evaluate the effects of doxorubicin and new anthracycline analogue on the heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050148
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    Effects of space flight on GLUT-4 content in rat plantaris muscle (1998)
    Springer
    International journal of biometeorology 41 (1998), S. 101-104 
    Details
    ISSN: 1432-1254
    Keywords: Key words Space flight ; Rat ; Plantaris muscle ; GLUT-4 ; Citrate synthase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geography , Physics
    Notes: Abstract  The effects of 14 days of space flight on the glucose transporter protein (GLUT-4) were studied in the plantaris muscle of growing 9-week-old, male Sprague Dawley rats. The rats were randomly separated into five groups: pre-flight vivarium ground controls (PF-VC) sacrificed approximately 2 h after launch; flight groups sacrificed either approximately 5 h (F-R0) or 9 days (F-R9) after the return from space; and synchronous ground controls (SC-R0 and SC-R9) sacrificed at the same time as the respective flight groups. The flight groups F-R0 and F-R9 were exposed to micro-gravity for 14 days in the Spacelab module located in the cargo bay of the shuttle transport system – 58 of the manned Space Shuttle for the NASA mission named ”Spacelab Life Sciences 2”. Body weight and plantaris weight of SC-R0 and F-R0 were significantly higher than those of PF-VC. Neither body weight nor plantaris muscle weight in either group had changed 9 days after the return from space. As a result, body weight and plantaris muscle weight did not differ between the flight and synchronous control groups at any of the time points investigated. The GLUT-4 content (cpm/µg membrane protein) in the plantaris muscle did not show any significant change in response to 14 days of space flight or 9 days after return. Similarly, citrate synthase activity did not change during the course of the space flight or the recovery period. These results suggest that 14 days of space flight does not affect muscle mass or GLUT-4 content of the fast-twitch plantaris muscle in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004840050060
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    Endosomes: another extra-mitochondrial location of type-1 porin/voltage-dependent anion-selective channels (VDAC) (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 478-480 
    Details
    ISSN: 1432-2013
    Keywords: Key words Chloride channel ; Endosomes ; Porin ; Rat ; Renal cortex ; Voltage-dependent anion channel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Endocytotic vesicles (EV) isolated from rat renal cortex were subjected to SDS-polyacrylamide gel electrophoresis and Western blotting. A monoclonal antibody against human type-1 porin (31 kDa) detected a strong band of 31 kDa. The same antibody has been used as the primary antibody in indirect immunocytochemistry. Light microscopy of cryostat sections of rat renal cortex showed a heavy staining of EV underneath the brush-border membrane. Electron microscopy was performed by ”preembedding immunogold staining” of rat renal cortex, the sections of which showed an extensive labelling of EV with gold particles. These results demonstrate that the expression of type-1 porin is not restricted to outer mitochondrial membranes. The biological function of endosomal type-1 porin has as yet to be ascertained.
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    URL: http://dx.doi.org/10.1007/s004240050659
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    Luminal ATP induces K+ secretion via a P2Y2 receptor in rat distal colonic mucosa (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 712-716 
    Details
    ISSN: 1432-2013
    Keywords: Key words ATP ; Distal colon ; Exocrine secretion ; K+ secretion ; Luminal receptors ; P2Y2 receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have previously investigated, in studies of rat distal colonic mucosa, the effect of ATP added to the basolateral side on ion transport and [Ca2+]i. It was demonstrated that ATP acts via a P2Y1 receptor to increase [Ca2+]i and NaCl secretion. In the present study we investigated the effect of luminally added nucleotides (ATP, UTP) on transepithelial voltage (V te) and resistance (R te) in Ussing chamber experiments on rat distal colonic mucosa. Both nucleotides induced a rapid and transient (within 30 s) change of V te to lumen-positive values (resting V te: –2±1 mV; peak V te after 100 µmol/l ATP: +2.4±1.1 mV) and a decrease of R te from 89.9±10.3 to 83.8±9.1 Ωcm2 (n=10). Similar values were obtained with luminal UTP (n=15). The estimated EC50 values for both nucleotides were approximately 6 µmol/l. The ATP-induced V te effect was nearly completely sensitive to Ba2+. Addition of the K+ channel blocker Ba2+ (1 mmol/l) to the luminal solution reversibly inhibited 77±4% (n=5) of the ATP-induced V te effect. Experiments to identify the respective P2 receptor subtype revealed the following rank order of potency at 500 µmol/l agonist: UTP≥ATP〉〉2-methylthio-ATP=ADP〉〉adenosine〉 AMP〉β,γ-methylene-ATP (n=5). This closely resembles the published rank order for the P2Y2 receptor. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique P2Y2 receptor-specific mRNA was detected in total RNA extracted from isolated crypts. In summary these data indicate that luminal ATP and UTP act via a P2Y2 receptor in the luminal membrane of colonic mucosa to elicit a transient K+ secretion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050693
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    The disruption of myofibre structures in rat skeletal muscle after forced lengthening contractions (1998)
    Springer
    Pflügers Archiv 436 (1998), S. 735-741 
    Details
    ISSN: 1432-2013
    Keywords: Key words Actin ; Cytoskeleton ; Desmin ; Dystrophin ; Fibronectin ; Muscle damage ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Specific antibodies against structural proteins (actin, desmin, dystrophin, fibronectin) of muscle fibres were used to study the effect of forced lengthening contractions on muscle microarchitecture. Tibialis anterior (TA) muscle of male Wistar rats were subjected to 240 forced lengthening contractions. At consecutive time points (0, and 6 h, 2, 4, and 7 days) after stimulation, the TA muscle was excised for biochemical and histological assays. β-Glucuronidase activity, a quantitative indicator of muscle damage, showed increased values 2–7 days after the lengthening, peaking on day 4 (11.7-fold increase). A typical course of histopathological changes (myofibre swelling, necrosis and regeneration) was observed. In immunohistochemistry, the earliest abnormality observed was discontinuous dystrophin staining in some swollen fibres immediately after commencement of exercise, while at the same time no alterations occurred in the staining of the other antibodies studied. Six hours later, all the swollen fibres were uniformly desmin as well as dystrophin negative. The great majority, but not all, of the swollen fibres showed disorganized actin staining and intramyocellular localization of fibronectin. The early phase disruption of myofibre structures as measured in this study provides evidence of their central role following damage in skeletal muscle. These results suggest that the sequence of structural changes in the route to muscle fibre necrosis in injury induced by forced lengthening contraction originates in the disruption of the plasma membrane and the intermediate filament, which leads to disturbances in the myofibrillar system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050696
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    Extracellular glutamate increases in rostral ventrolateral medulla during static muscle contraction (1998)
    Springer
    Pflügers Archiv 435 (1998), S. 465-471 
    Details
    ISSN: 1432-2013
    Keywords: Key words Arterial pressure ; Microdialysis ; Excitatory amino acid ; Exercise ; Pressor Reflex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The ventrolateral medulla is an important site involved in increases in arterial pressure and heart rate during static muscle contraction. Glutamate, an excitatory amino acid neurotransmitter, appears to play a role in mediating these responses. We measured glutamate concentration in the extracellular fluid of the rostral ventrolateral medulla during static muscle contraction in anesthetized rats. A 2-min tibial nerve stimulation-evoked muscle contraction increased blood pressure by 30 ± 4 mmHg and heart rate by 32 ± 4 bpm. Extracellular glutamate in the rostral ventrolateral medulla also increased from 9 ± 1 pmol/4 μl to 14 ± 1 pmol/4 μl. Results were repeatable over two subsequent contractions. Tibial nerve stimulation following neuromuscular blockade did not elicit changes in blood pressure, heart rate or extracellular fluid glutamate. Data demonstrate that muscle contraction increases extracellular fluid concentration of glutamate in the rostral ventrolateral medulla, suggesting that rostral ventrolateral medullary glutamate release is a neurochemical change associated with cardiovascular responses during static muscle contraction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004240050540
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    Expression of sucrase and intestinal-type alkaline phosphatase in colorectal carcinoms in rats treated with methylazoxymethanol acetate (1998)
    Springer
    Journal of cancer research and clinical oncology 124 (1998), S. 677-682 
    Details
    ISSN: 1432-1335
    Keywords: Key words Small-intestine phenotype ; Sucrase ; Intestinal-type alkaline phosphatase ; Colon cancer ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004320050231
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    Stimulation of forward locomotion by SCH-23390 and raclopride in d-amphetamine-treated rats (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 593-599 
    Details
    ISSN: 1432-1912
    Keywords: Key words d-amphetamine ; Dopamine receptors ; Locomotor activity ; Raclopride ; SCH-23390 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In d-amphetamine-treated (4.0 mg kg–1 s.c.) rats the selective dopamine D1 and D2/3 receptor antagonists SCH-23390 (2.5–20.0 µg kg–1 s.c.) and raclopride (12.5–100.0 µg kg–1 s.c.), respectively, produced a biphasic pattern of effects on forward locomotion, as observed in an open-field arena (≈0.5 m2). Thus, at the low doses of SCH-23390 (2.5–10.0 µg kg–1) or raclopride (12.5–50.0 µg kg–1), there was a statistically significant increase in forward locomotion, followed by suppression of the behavior at the higher doses. The SCH-23390-induced (5.0 µg kg–1) stimulation of forward locomotion was partially antagonized by concomitant raclopride treatment (12.5–25.0 µg kg–1) and the corresponding raclopride-induced (12.5 µg kg–1) stimulation was fully antagonized by treatment with SCH-23390 (2.5–5.0 µg kg–1). Furthermore, the SCH-23390- or raclopride-induced stimulation of forward locomotion was also antagonized by treatment with the α1-adrenoceptor antagonist prazosin (1.0 mg kg–1 s.c.). These observations suggest that under conditions of an increased general tone at brain dopamine receptors, there is a mutual inhibitory synergy between dopamine D1 and D2/3 receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005213
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    Morphologic and functional consequences of intimal hyperplasia in the rat carotid artery (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 133-142 
    Details
    ISSN: 1432-1912
    Keywords: Key words Intimal hyperplasia ; Potassium chloride ; α1-Adrenoceptor ; Methacholine ; Sodium nitroprusside ; Rat ; Carotid artery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of neointima formation on functional characteristics was investigated in rat carotid artery preparations. The process of intimal hyperplasia development in the injured carotid arteries was followed in time both morphologically and morphometrically. Simultaneously with the loss of endothelial cells due to the balloon injury procedure, the vasodilator responses to methacholine were abolished. The sensitivity for the α1-adrenoceptor agonist phenylephrine appeared to be increased only immediately after injury. The balloon injury method led to significant neointima formation in the rat left common carotid artery 14 days after the intervention. Eight weeks after balloon injury, the neointimal mass reached its maximum. Parallel to the development of intimal hyperplasia, the α1-mediated vasoconstrictor responses to phenylephrine were significantly impaired. After 12 weeks of observation, reoccurrence of mature endothelial cells on the luminal surface of the neointima could be observed. Simultaneously, the vascular responses to phenylephrine and methacholine recovered. The vasoconstrictor responses to high potassium concentrations (100 mM) as well as the vasodilator effects of sodium nitroprusside appeared to be uninfluenced by balloon injury throughout the period of observation. From this study we conclude that both the receptor-mediated contractile responses to α1-adrenoceptor stimulation and the endothelium-dependent vasodilator responses to methacholine become severely impaired as a consequence of balloon catheter injury followed by intimal hyperplasia. However, these pharmacological responses may fully recover upon a prolonged period of endothelial regeneration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005147
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    U-83836E prevents kainic acid-induced neuronal damage (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 413-418 
    Details
    ISSN: 1432-1912
    Keywords: Key words PBR ; Kainate ; Reactive oxygen species ; Glutamate ; U-83836E ; Mitochondria ; Cerebellum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%±35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10–9 to 5×10–6M) completely inhibited this increase, with an IC50 value of 3.02±1.08×10–7M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1±0.8μM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicityin vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341±192fmol mg–1. When U-83836E was coadministered with KA, the Bmax was reduced to 765±122fmol mg–1, which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518±33fmol mg–1). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005187
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    Investigation of the influence of pregnancy on the role of nitric oxide in gastric emptying and non-adrenergic non-cholinergic relaxation in the rat (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 671-676 
    Details
    ISSN: 1432-1912
    Keywords: Key words Gastric emptying ; Nitric oxide ; Pregnancy ; Gastric fundus ; Pylorus ; Non-adrenergic non-cholinergic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of pregnancy on the role of nitric oxide (NO) in gastric emptying and in non-adrenergic non-cholinergic (NANC) relaxation was studied in rats. The gastric emptying of a non-nutrient liquid solution and of polysterene beads was studied in non-pregnant (NP), 6 to 7 days pregnant (P7) and 18 to 20 days pregnant (P20) rats. Longitudinal muscle strips of the gastric fundus and circular muscle strips of the pylorus were isolated from NP and P20 rats and NANC relaxations were induced by electrical field stimulation. The gastric emptying of the liquid meal was significantly increased in P20 rats as compared to NP and P7 rats. In NP rats, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently (50–150 mg/kg ip) reduced the gastric liquid emptying; the inhibitory effect of 100 mg/kg L-NAME ip was prevented by 400 mg/kg ip L-arginine and was mimicked by 100 mg/kg NG-monomethyl-L-arginine (L-NMMA). The percentage inhibition of the liquid emptying by L-NAME did not differ between the 3 groups, except for the dose of 150 mg/kg ip where it was significantly lower in P20 rats. The gastric emptying of beads was 54% in NP, 36% in P7 and 69% in P20 rats but these values were not significantly different illustrating the great variability. The inhibitory effect of L-NAME (25 and 100 mg/kg ip) on the emptying of beads did not differ between the 3 groups. As evaluated in NP rats, the inhibitory effect of L-NAME on the gastric emptying of the beads was not prevented by L-arginine nor mimicked by L–NMMA. Electrical field stimulation in NANC conditions induced frequency-dependent relaxations in the fundus strips and relaxations followed by rebound contractions in the pyloric strips. These electrically induced NANC relaxations and their reduction by 3×10–4 M L-NAME were not different between NP and P20 rats. It can be concluded that no evidence for a regulatory role of NO in the gastric emptying of the beads was found, and that the nitrergic contribution to the gastric emptying of liquids and to the fundic and pyloric NANC relaxations was not influenced by pregnancy in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005223
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    Oxytocin increases the survival of musculocutaneous flaps (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 701-704 
    Details
    ISSN: 1432-1912
    Keywords: Key words Oxytocin ; Rat ; Musculocutaneous flap ; Wound healing ; Oxytocin antagonist ; Growth factors ; IGF-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to evaluate the effect of oxytocin on survival of musculocutaneous flaps in male Sprague-Dawley rats. For this purpose oxytocin (0.1 or 1.0 mg/kg), an oxytocin antagonist (1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin) (1.0 mg/kg) alone or in combination with oxytocin (1.0 mg/kg) or saline was given subcutaneously (s.c.), 24 hours and 1 hour before and 24 hours after flap surgery. In addition, oxytocin (1 µg/kg) or saline was given intracerebroventricularly (i.c.v.) according to the same schedule. Six days after surgery the amount of viable tissue was measured. Oxytocin 1.0 (but not 0.1) mg/kg s.c. and 1.0 µg/kg i.c.v. increased survival of the flaps (s.c.: 13.8±14.6% versus 6.10±5.45%; p〈0.05 and i.c.v.: 25.5±14.0% versus 10.3±5.79%; p〈0.01). This effect was abolished by the oxytocin antagonist. Furthermore, the oxytocin-treated rats had significantly higher plasma levels of insulin-like growth factor-1 (IGF-1) (p〈0.05). These data indicate that oxytocin increases the survival of musculocutaneous flaps. The effect seems to be exerted within the central nervous system since a 1000 fold lower dose of oxytocin given i.c.v. increased flap survival to the same extent as the s.c. given dose. IGF-1 might be one of the mediators of this effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005227
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    Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver (1998)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 357 (1998), S. 336-343 
    Details
    ISSN: 1432-1912
    Keywords: Key words NNK ; Elimination kinetics ; Metabolism ; Perfusion ; Lung ; Liver ; Rat ; N-oxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via α-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 ± 1.6 ml/min, half-life 14.6 ± 1.2 min) than by lung (clearance 2.1 ± 0.5 ml/min, half-life 47.9 ± 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK α-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of α-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 μM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via α-hydroxylation for this high concentration of NNK.
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    URL: http://dx.doi.org/10.1007/PL00005176
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    Rat models of normocalcemic hypercalciuria of different pathogenic mechanisms (1998)
    Springer
    Pediatric nephrology 12 (1998), S. 201-205 
    Details
    ISSN: 1432-198X
    Keywords: Key words: Hypercalciuria ; Idiopathic hypercalciuria ; 1 ; 25-Dihydroxyvitamin D ; Furosemide ; Ammonium chloride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Hypercalciuria was induced in female Sprague-Dawley rats, aged 40±2 days, by 7-day administration (mean±SEM) of calcitriol (5.4±0.1 ng/100 g per day, intraperitoneal), furosemide (14.9±1.9 mg/100 g per day, oral), or ammonium chloride (3.8±0.1 mEq/100 g per day, oral). Calciuria increased from 1.9±0.2, 1.6±0.2, and 1.9±0.3 to 5.4±0.5, 4.0±0.9, and 5.4±0.5 mg/100 g per day in the calcitriol (VD, n = 9), furosemide (F, n = 6), and ammonium chloride (AC, n = 10) groups, respectively. Calciuria did not change (1.9±0.3 vs. 1.6±0.1 mg/100 g per day) in control rats (n = 8). Ninety-six percent of treated rats became hypercalciuric as assessed by urine calcium excretion above the 90th percentile of normal values. Hypercalciuria was of similar degree in the three groups of rats and was not associated with hypercalcemia, metabolic acidosis, severe serum electrolyte imbalance, or growth impairment. VD rats had low serum parathyroid hormone (PTH) concentrations (3.0±0.5 pg/ml vs. 15.8±1.3 pg/ml in controls, P 〈0.05), whereas serum PTH was not significantly elevated in F rats (16.2±1.8 pg/ml). Thus, the protocol caused three forms of hypercalciuria that mimicked the clinical conditions of idiopathic hypercalciuria in humans and may clearly be differentiated according to their mechanism of production. This experimental model of normocalcemic hypercalciuria may be useful to clarify unknown aspects of pathogenesis and pathophysiology of idiopathic hypercalciuria in children.
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    URL: http://dx.doi.org/10.1007/s004670050437
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    Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action (1998)
    Springer
    Psychopharmacology 137 (1998), S. 292-302 
    Details
    ISSN: 1432-2072
    Keywords: Key words mCPP (m-chlorophenylpiperazine) ; Drug discrimination ; 5-HT2C ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous drug discrimination studies with the serotonergic drug m-chlorophenylpiperazine (mCPP) showed conflicting results, with some authors concluding that the cue was mediated by 5-HT2C receptors, but others that it was definitively not. We further examined the discriminative stimulus properties of mCPP in rats and reviewed previously published data. We trained rats to discriminate mCPP (2.0 mg/kg, PO) from water. We found that the mCPP cue generalized to m-trifluoromethyl-phenylpiperazine (TFMPP) and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and partially to eltoprazine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine and trazodone. A moderate level of generalization was obtained with quipazine, 1-(m-chlorophenyl)biguanide and clonidine. No generalization was found with flesinoxan, methiothepin, idazoxan and haloperidol. Mianserin and methysergide antagonized the mCPP stimulus, whereas ketanserin antagonized it partially. Metergoline, methiothepin and clozapine only marginally antagonized the mCPP stimulus. These results show that the discriminative stimulus effects of mCPP are predominantly mediated by 5-HT2C receptors, and to some extent by 5-HT1B receptors. When considering our results and other research together, the substitution tests clearly point to a 5-HT2C receptor mediated stimulus, with an additional role for 5-HT1B receptors. Antagonism studies are less clearcut, but are also suggestive of a 5-HT2C receptor mediated effect. A definitive answer as to whether other receptors, e.g. 5-HT2B and 5-HT7, are of any importance in mCPP’s discriminative stimulus properties has to wait for more selective ligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050622
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    Neonatal clomipramine treatment, alcohol intake and circadian rhythms in rats (1998)
    Springer
    Psychopharmacology 138 (1998), S. 176-183 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Antidepressant ; Circadian ; Clomipramine ; Neonatal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neonatal exposure to antidepressant monoamine re-uptake inhibitors produces a wide variety of effects on the behavior and physiology of adult rats which are consistent with features of clinical depression. Since depressed patients show characteristic alterations in circadian rhythmicity, our laboratory has examined free-running circadian drinking rhythms in this putative animal depression model. Previously, neonatal desipramine treatment was shown to lengthen free-running period, and increase circadian amplitude, spectral magnitude, and voluntary alcohol intake (10% ethanol v/v) of male rats. The purpose of the present study was to examine the effects of neonatal clomipramine treatment (25 or 30 mg/kg SC, postnatal days 8–21) on circadian drinking rhythms and alcohol intake of both male and female rats. In addition, effects of alcohol exposure on circadian rhythmicity were also examined. Contrary to expectations, free-running period of clomipramine-treated rats did not differ from saline-treated controls in either constant darkness (DD) or constant light (LL), but spectral magnitude was increased in clomipramine-treated males and females, and circadian amplitude was increased in clomipramine-treated females. Neonatal clomipramine also increased voluntary alcohol intake, and both clomipramine- and saline-treated groups displayed significant period-shortening during alcohol exposure. Taken together, these results suggest that alterations in the amplitude and coherence of circadian rhythmicity may be more consistent than alterations in free-running period in animal depression models, as has been suggested previously for depressed patients.
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    URL: http://dx.doi.org/10.1007/s002130050660
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    Activation of midline thalamic nuclei by antipsychotic drugs (1998)
    Springer
    Psychopharmacology 135 (1998), S. 37-43 
    Details
    ISSN: 1432-2072
    Keywords: Key wordsNeuroleptics ; Antipsychotic drugs ; Thalamus ; Fos immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The thalamus has been proposed as a site which may be involved in the production of the syndrome of schizophrenia and the response of schizophrenic symptoms to treatment. These studies test whether, consistent with this hypothesis, the activation of thalamic nuclei is a shared property of neuroleptic antipsychotic drugs. Rats were given single doses of the typical high and low potency neuroleptics haloperidol (1 mg/kg) and chlorpromazine (20 mg/kg), the atypical neuroleptics thiroridazine (20 mg/kg) and clozapine (20 mg/kg), the specific dopamine antagonist raclopride (3 mg/kg), the mixed dopamine/serotonin antagonist risperidone (3 mg/kg) or drug-free vehicle. Increased expression of Fos-like protein was utilized as a marker of cellular activation. All drugs tested, including typical and atypical antipsychotic agents, led to similar effects on the midline thalamic paraventricular, centromedian and rhomboid nuclei and the nucleus reuniens. These results suggest that midline thalamic nuclei may participate in neural circuits mediating some of the shared effects of antipsychotic drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050483
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    Ethanol and N-methyl-D-aspartate receptor complex interactions: a detailed drug discrimination study in the rat (1998)
    Springer
    Psychopharmacology 135 (1998), S. 44-51 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Rat ; Ethanol ; NMDA receptor ; AMPA receptor ; Dizocilpine ; Memantine ; Phencyclidine ; N-allyl-normetazocine ; Pentazocine ; Arcaine ; Polyamine site ligand ; Glycine site ligand
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The discriminative stimulus properties of compounds that interact with the NMDA receptor complex were investigated in rats trained to discriminate ethanol from saline. Male Wistar rats were trained in a two-lever operant drug discrimination paradigm to make differential responses [fixed ratio 10 (FR10)] for food after ethanol (1 g/kg IP; 12% v/v ethanol solution) and saline vehicle injections. Drug effects were assessed by means of generalization and antagonism tests. In the generalization tests, the noncompetitive NMDA antagonists acting at the ion channel dizocilpine, memantine, phencyclidine (PCP) and the sigma1 receptor agonists (+)-pentazocine and (+)-N-allyl-normetazocine (NANM) dose-dependently generalized for ethanol, whereas the α-amino-3-hydroxy- 5-methyl-4-isoxazole-propionate (AMPA) antagonist GYKI 52466, the glycine antagonists L-701,324 and MRZ 2/502, the polyamine site antagonist arcaine and the polyamine site ligand spermidine, did not. Our results show that the noncompetitive NMDA antagonists fully substitute dose-dependently for ethanol in a drug-discrimination task. The ethanol-like discriminative stimulus effects of PCP, pentazocine and NANM, which are also sigma receptor ligands, are likely to be attributed to their activity at NMDA receptors. We therefore assume that some of the acute effects of ethanol are mediated via NMDA receptor antagonism at the PCP binding site.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050484
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    Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency (1998)
    Springer
    Psychopharmacology 136 (1998), S. 83-90 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Self-administration ; Dose ; Contingency ; Yoking ; Feeding ; Rat ; Sprague-Dawley
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050542
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    Lack of sensitization to the effects of d-amphetamine and apomorphine on sensorimotor gating in rats (1998)
    Springer
    Psychopharmacology 135 (1998), S. 296-304 
    Details
    ISSN: 1432-2072
    Keywords: Key words Prepulse inhibition ; Sensorimotor gating ; Sensitization ; Locomotor activity ; Amphetamine ; Apomorphine ; Schizophrenia ; Startle ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study assessed whether repeated injections of d-amphetamine or apomorphine could induce sensitization to the disruptive effects of these psychomotor stimulants on sensorimotor gating in rats. In the first experiment, rats were given six pre-exposures to either 2.0 mg/kg d-amphetamine or saline before being tested for the effects of d-amphetamine (0.0, 0.5, 1.0, 2.0 or 4.0 mg/kg, IP) on prepulse inhibition of acoustic startle (PPI) and locomotor activity. The tests for PPI confirmed that sensorimotor gating could be disrupted by a high dose of d-amphetamine (4.0 mg/kg). However, comparison of the dose-response curves for the drug and saline pre-exposed groups did not reveal evidence for sensitization to this d-amphetamine effect in drug-pre-exposed rats, despite indications that sensitization had developed to the locomotor stimulant effects of d-amphetamine. A similar pattern of results was obtained in a second experiment that examined the effects of apomorphine (0.0, 0.1, 0.2, 0.4 and 0.8 mg/kg, SC) on PPI and locomotion in rats pre-exposed to 2.0 mg/kg of this drug or its vehicle. These findings demonstrate that treatments which induce sensitization to the behavioral activating effects of psychomotor stimulants do not necessarily produce sensitization to the disruptive effects of stimulants on sensorimotor gating. The implications of these results for hypotheses linking sensitization-like processes to the etiology of schizophrenia are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050513
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    Repeated administration of ephedrine induces behavioral sensitization in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 52-56 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Dopamine ; Ephedrine ; Locomotion ; Rat ; Sensitization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Systemic injection of the sympathomimetic agent ephedrine (EPH) stimulates locomotion in drug-naive rats, an effect that may be dependent on the enantiomer of EPH employed [(–)-EPH or (+)-EPH]. The present experiments examined the effects of repeated EPH exposure on locomotion in rats to assess whether these treatments result in drug tolerance or sensitization. In experiment 1, adult male rats were injected once daily with 0, 10, 20, or 40 mg/kg (–)-EPH (IP) on each of 11 days. Locomotor activity was assessed for 60 min after drug injection. Acute exposure to (–)-EPH treatment increased locomotion for animals receiving 20 or 40 mg/kg, and this effect was augmented after 11 days of drug administration. A vehicle-only injection was given to all animals on day 12 to determine the influence of environmental cues on sensitization. On day 13, all rats were injected with 10 mg/kg cocaine HCl to assess whether repeated (–)-EPH exposure produced a cross-sensitization to cocaine (10 mg/kg, IP). Only rats treated repeatedly with 40 mg/kg (–)-EPH exhibited increases in cocaine-stimulated locomotion relative to saline-treated rats. In experiment 2, repeated exposure to (+)-EPH, 40 mg/kg, but not 20 mg/kg, increased activity and demonstrated the development of sensitization. Cross-sensitization to cocaine (10 mg/kg, IP) was not evident following treatment with either concentration of (+)-EPH. There was no evidence that contextual events alone played a role in the effects observed here.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050738
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    Tolerance and cross-tolerance to the rate-suppressing effects of opioids in butorphanol-treated rats: influence of maintenance dose and relative efficacy at the mu receptor (1998)
    Springer
    Psychopharmacology 140 (1998), S. 57-68 
    Details
    ISSN: 1432-2072
    Keywords: Key words Butorphanol ; Cross tolerance ; Dependence ; Relative efficacy ; Opioid ; Rat ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of the present investigation was to examine the development of tolerance to the rate-suppressing effects of mu and kappa opioids in rats administered either 3.0 (low) or 30 (high) mg/kg per day of butorphanol, an opioid with low relative efficacy at the mu receptor. The mu opioids butorphanol, buprenorphine, morphine, fentanyl and sufentanil, and the kappa opioid U50,488 dose-dependently suppressed responding under all conditions examined. In rats administered the low maintenance dose of butorphanol, tolerance developed to the effects of butorphanol, buprenorphine and morphine, but not to fentanyl and sufentanil. In rats administered the high maintenance dose, tolerance developed to all of the mu opioids examined. In both treatment groups, the degree to which tolerance developed was greater for butorphanol and buprenorphine than for morphine, fentanyl and sufentanil; and the degree to which tolerance developed to these mu opioids was greater in rats administered the high maintenance dose of butorphanol. The tolerance that developed to morphine, fentanyl and sufentanil was not altered when tested at both 23 and 47 h following the previous maintenance dose of butorphanol, suggesting that these changes were not due to any acute pharmacological interactions between butorphanol and the test compound (i.e., antagonism). Tolerance was also conferred to the kappa opioid U50,488 in both groups of rats, and in rats administered the high maintenance dose, this effect was obtained when tested 23 and 47 h following the previous maintenance dose of butorphanol. Physical dependence developed in rats administered the high maintenance dose of butorphanol, as evidenced by the development of enhanced sensitivity to the rate-suppressing effects of naloxone, and the finding that 30 mg/kg naloxone decreased body weight in a time-dependent manner. No physical dependence was apparent in rats administered the low maintenance dose of butorphanol. These data suggest that during chronic treatment with butorphanol, (1) greater degrees of tolerance are conferred to drugs possessing low efficacy at the mu opioid receptor, (2) tolerance is enhanced as the maintenance dose of the toleragen is increased, and (3) mu-opioid tolerance may be observed under conditions that do not produce mu-opioid dependence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050739
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    Haloperidol, raclopride, and eticlopride induce microcatalepsy during operant performance in rats, but clozapine and SCH 23390 do not (1998)
    Springer
    Psychopharmacology 140 (1998), S. 81-90 
    Details
    ISSN: 1432-2072
    Keywords: Key words Neuroleptics ; Dopamine receptor ; Catalepsy ; EPS ; Antipsychotic drug ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The purpose of this work was (1) to assess the ability of selected antipsychotic and comparison drugs to induce arrest of movement phenomena during operant responding and (2) to evaluate the capacity of muscarinic anitcholinergics to block such effects. The effects of haloperidol (0.02–0.12 mg/kg, IP, 45 min), raclopride (0.05–0.80 mg/kg, IP, 30 min) eticlopride (0.02–0.16 mg/kg, IP, 45 min), clozapine (1.0–8.0 mg/kg, IP, 60 min) and SCH 23390 (0.01–0.16 mg/kg, IP, 30 min) were administered to rats for 4 weeks in a between-groups dosing design. Operant responses in 15 min and the maximum duration of the rat’s muzzle entry into the reinforcement dipper well (the measure of arrest of movement that reflected microcatalepsy) were the quantitative measures of behavior. The D2 antagonists dose-relatedly decreased operant responding and increased maximum muzzle duration, effects that were significantly reversed by the anticholinergic scopolamine (0.1 mg/kg) or atropine (6.0 mg/kg). Although the atypical antipsychotic drug clozapine and the selective D1 antagonist SCH 23390 both significantly reduced operant responding, these drugs did not produce microcatalepsy. The results suggested that microcatalepsy expressed in the context of ongoing operant behavior may model low-dose extrapyramidal side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050742
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    Evidence that GABA transmission mediates context-specific extinction of learned fear (1998)
    Springer
    Psychopharmacology 140 (1998), S. 105-115 
    Details
    ISSN: 1432-2072
    Keywords: Key words FG 7142 ; β-Carboline ; Benzodiazepine inverse agonist ; Latent inhibition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Six experiments used rats to study the effects of the β-carboline FG 7142 on extinction of fear responses (freezing) to an auditory cue that had signalled footshock. Subcutaneous injection of FG 7142 interfered with the development of extinction without having any detectable effect on the rats’ levels of fear prior to extinction. Injection of FG 7142 also reversed extinction, partially reinstating fear responses that had been extinguished previously. A similar reinstatement of extinguished fear was seen when rats were tested for fear of the cue in a different chamber. The reinstatement produced by FG 7142 and that caused by context shift were not additive: FG 7142 did not increase extinguished fear if rats were tested in the different chamber. Finally, FG 7142 had no detectable effect on the latent inhibition of fear produced by repeatedly presenting the cue alone before conditioning with shock, even though this inhibition, like extinction, was affected by a shift in context. The present findings indicate that GABA transmission at GABAA receptors is involved in the inhibition of extinguished fear, and that this effect of GABA is regulated by those cues that constitute the extinction context.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050745
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    Preclinical evaluation of the reinforcing and discriminative stimulus effects of agomelatine (S-20098), a melatonin agonist (1998)
    Springer
    Psychopharmacology 140 (1998), S. 503-509 
    Details
    ISSN: 1432-2072
    Keywords: Key words Agomelatine ; S-20098 ; Melatonin ; Diazepam ; Methohexital ; Drug discrimination ; Self-administration ; Substance abuse evaluation ; Monkey ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Agomelatine (S-20098), an analog of melatonin, has shown promise as a chronobiotic in animal models of sleep phase disorders and is being developed for clinical use. Previous research has shown that the pharmacological profile of melatonin-like drugs overlaps that of γ-amino butyric acid (GABA) agonists. Given the potential of drugs within the latter class for recreational abuse in humans, evaluation of this potential for melatonin analogs that target similar therapeutic indications is important. In the present study, agomelatine was tested in animal models of the subjective and reinforcing effects of CNS depressant drugs; i.e., diazepam discrimination in rats and IV methohexital self-administration in rhesus monkeys, respectively. Neither agomelatine nor melatonin substituted for diazepam in rats trained to discriminate 2.5 mg/kg diazepam from vehicle. Further, agomelatine was not self-administered by rhesus monkeys. These results suggest that agomelatine would not produce diazepam-like intoxication in humans, nor would it likely be subject to abuse.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050795
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    The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate (1998)
    Springer
    Psychopharmacology 140 (1998), S. 510-518 
    Details
    ISSN: 1432-2072
    Keywords: Key words Animal model ; Addiction ; Loss of control ; Dependence ; Withdrawal ; d-Amphetamine ; Opiate ; Alcohol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37 ± 0.02 mg/kg per day, subordinate rats: 0.57 ± 0.05 mg/kg per day) and environmental variables (group housing: 0.21 ± 0.02 mg/kg per day, single housing: 0.41 ± 0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9 ± 0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6 ± 0.6 mg/kg per day; age-matched controls: 0.37 ± 0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1 ± 0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42 ± 0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050796
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    Δ9-THC training dose as a determinant for (R)-methanandamide generalization in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 519-522 
    Details
    ISSN: 1432-2072
    Keywords: Key words Δ9-THC ; Cannabinoids ; (R)-methanandamide ; Anandamides ; Efficacy ; Drug discrimination ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than Δ9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% Δ9-THC responses in the two lower Δ9-THC training dose conditions. However, only around 60% Δ9-THC responses occurred in the 5.6 mg/kg Δ9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer Δ9-THC-appropriate responses in this group. Morphine did not substitute for Δ9-THC. In conclusion, the data with Δ9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.
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    URL: http://dx.doi.org/10.1007/s002130050797
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    Prevention of lithium nephrotoxicity in a novel one-hour model in rats (1998)
    Springer
    Psychopharmacology 138 (1998), S. 34-39 
    Details
    ISSN: 1432-2072
    Keywords: Key words Lithium ; Nephrotoxicity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It is well established that lithium can cause morphologically visible damage to the kidneys of humans and animals. Although the clinical significance of its nephrotoxicity is debatable, it would be desirable to find a method to prevent lithium’s effect on the kidneys. Toward this end, we have developed a novel method for producing nephrotoxicity that will be useful for research on prevention. A single, large, toxic dose of lithium chloride (LiCl) caused necrosis of the distal convoluted tubules, which was visible by light microscopy in 30 min, had fully developed in 1 h, and had disappeared by the next day. The lesions were seen after IP or IV injections of fasted rats of three different strains. Equivalent doses of NaCl, KCl, MgCl2 and combinations thereof had no such effect, nor did they inhibit nephrotoxicity when incorporated into the LiCl solution. However, relatively small doses of LiCl injected by any route 3 or 24 h beforehand prevented the nephrotoxicity. The mechanism of prevention is not known, but it does not involve reduction of lithium levels in the kidneys.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050642
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    Repeated tail pinch leads to desensitization of postsynaptic α2-adrenoceptors which modulate the jaw-opening reflex in the rat (1998)
    Springer
    Psychopharmacology 138 (1998), S. 96-101 
    Details
    ISSN: 1432-2072
    Keywords: Key words Jaw-opening reflex ; α2-Adrenoceptor sensitivity ; Tail pinch ; Repeated stress ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There are few in vivo studies which have investigated the modulation of central postsynaptic α 2-adrenoceptors functionality provoked by stress. We assessed in the rat the effects of either single or repeated tail pinch on clonidine-induced inhibition of the jaw-opening reflex (JOR) via activation of postsynaptic central α 2-adrenoceptors. At the end of each experimental period, the progressive inhibition of the digastric electromyographic responses elicited by orofacial electrical stimulation after the IV administration of cumulative doses (× 3.3) of clonidine (0.1–10 000 μg/kg) was recorded. Single tail pinch did not significantly modify the ability of the agonist to inhibit the JOR, although there was a tendency to decrease the basal amplitude of the reflex (a 40% reduction) immediately after exposure to the single stressor. However, the dose-response curve for clonidine-induced inhibition of the JOR was clearly shifted to the right in rats exposed to repeated tail pinch (ED50 was increased by 152%, P 〈 0.0001) when compared with the unstressed control group, without affecting the slope of the inhibitory function and the estimated maximum effect for the agonist. These results show that repeated stress leads to a subsensitivity of the α 2-adrenoceptors which modulate the JOR, suggesting the development of adaptive mechanisms in postsynaptic α 2-adrenoceptors in response to stress.
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    URL: http://dx.doi.org/10.1007/s002130050650
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    Evidence for behavioral sensitization to cocaine in preweanling rat pups (1998)
    Springer
    Psychopharmacology 138 (1998), S. 114-123 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Behavioral sensitization ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While chronic intermittent administration of stimulants often induces behavioral sensitization in adulthood, stimulant sensitization has rarely been reported prior to weaning [around postnatal day (P) 21]. Consistent pairing of drug administration with the test context often facilitates sensitization in adults, yet young animals have been typically returned to the home cage immediately post-injection. To determine whether promoting context-dependent sensitization might facilitate expression of sensitization in preweanlings, Sprague-Dawley rats were injected daily from P14 to P20 with 0, 5, 15, or 30 mg/kg cocaine HC1 and placed for 30 min in either the experimental chamber or home cage. On P21 (test day), subjects were challenged with either 15 mg/kg cocaine or saline prior to placement in the experimental chamber. Significant sensitization of cocaine-induced stereotyped head movements was evident in animals given 15 or 30 mg/kg chronically in the experimental chamber, but not when these same doses were given in the home cage. Less consistent evidence for cocaine-induced sensitization was seen when examining locomotion, although trends for sensitization of this behavior were seen in animals chronically injected in either the test chamber or home cage. Thus, preweanlings can exhibit cocaine sensitization, particularly in terms of stereotypy, when tested shortly after the chronic exposure period, with expression of this sensitization being facilitated by pairing the chronic injections with the test context.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050653
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    Sabcomeline (SB-202026), a functionally selective M1 receptor partial agonist, reverses delay-induced deficits in the T-maze (1998)
    Springer
    Psychopharmacology 138 (1998), S. 275-282 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alzheimer’s disease ; T-maze ; Conditioned taste aversion ; Muscarinic agonists ; Sabcomeline ; SB-202026 ; THA ; RS86 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Sabcomeline, (SB-202026 [R-(Z)-α-(methoxyimino)-1-azabicyclo [2.2.2] octane-3-acetonitrile]), a functionally selective muscarinic M1 receptor partial agonist, was tested in rats trained to perform a delayed, reinforced alternation task in a T maze, a test of short-term spatial memory. For comparison the cholinesterase inhibitor tacrine (THA-9-amino-1,2,3,4-tetrahydroaminoacridine) and the non-selective muscarinic receptor agonist RS86 (2-ethyl-8-methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) were also tested and all three compounds were also compared using a conditioned taste aversion (CTA) task. Sabcomeline (0.001–1.0 mg/kg IP) significantly reversed the T-maze choice accuracy deficit induced by a 20-s delay at 0.03 and 0.1 mg/kg. RS86 (0.1–3.0 mg/kg IP) reversed the deficit at 1.0 mg/kg and THA (0.1–3.0 mg/kg IP) had no effect at any dose. All three compounds induced conditioned taste aversion with minimum effective doses (MED) of 0.3, 1.0 and 3.0 mg/kg, respectively. The results show that sabcomeline reverses delay induced deficits in T-maze choice accuracy in a rewarded alternation task at doses approximately 10 times lower than those required to induce conditioned taste aversion. RS86 was equipotent in both tests. These data support the findings of clinical studies which have shown that SB-202026 provides significant symptomatic improvement in patients with probable Alzheimer’s disease at doses which do not induce cholinergic side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050672
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    The pharmacology of impulsive behaviour in rats III: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and ethanol on a paced fixed consecutive number schedule (1998)
    Springer
    Psychopharmacology 138 (1998), S. 295-304 
    Details
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Rat ; Imipramine ; Ethanol ; Haloperidol ; Chlordiazepoxide ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The behavioural trait of impulsivity may be made up of different components, including rapid decision making, intolerance to the delay of reward and a tendency to terminate chains of responses prematurely. It has been proposed to measure the last of these in rats using fixed consecutive number (FCN) schedules. The present study uses a modified version of the FCN procedure in which responding was paced by retracting the response lever for short periods between presses. In this way, the experimenter could control the maximum rate of responding. The procedure was made up of two components based on an FCN 8 schedule of food reinforcement. In the Fast component, lever presses were spaced by a minimum of 2 s and in the Slow component by a minimum of 5 s. The average chain length was significantly shorter, and the rats were less efficient in the Slow component. Five drugs were tested on this baseline, imipramine (1.0–10.0 mg/kg), ethanol (300–3000 mg/kg administered PO), haloperidol (0.01–0.1 mg/kg), chlordiazepoxide (1.0–10.0 mg/kg) and d-amphetamine (0.2–0.8 mg/kg). All the drugs reduced responding at the highest dose, but imipramine was different from the others in that it increased the average number of responses in the chain and produced a shift in the chain length distribution to the right, possibly reflecting a reduction in impulsivity. The other four drugs reduced chain length at the highest dose, although in the case of ethanol this effect was very small and, unlike the other three drugs, did not result in a shift in the distribution to the left. The paced FCN procedure can differentiate the effects of different drugs on one aspect of impulsivity, and is likely to be a useful procedure for further study of this aspect of behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050674
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    The pharmacology of impulsive behaviour in rats II: the effects of amphetamine, haloperidol, imipramine, chlordiazepoxide and other drugs on fixed consecutive number schedules (FCN 8 and FCN 32) (1998)
    Springer
    Psychopharmacology 138 (1998), S. 283-294 
    Details
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Amphetamine ; Antidepressant ; Haloperidol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The effects of drugs on one aspect of impulsive behaviour were evaluated using a schedule in which rats were trained to complete a fixed consecutive number of responses on one of two levers before pressing the second to obtain a reinforcer (FCN). Terminating the chain before completing the FCN resulted in the omission of the food, and can be considered an impulsive decision. Two groups of food-deprived rats were trained to press either 8 or 32 times on the left lever (FCN lever) of a two lever operant chamber before pressing the right lever (Reinforcement lever) to deliver a food pellet. Responding on the Reinforcement lever before completion of the sequence resulted in a short time-out and the rat had to begin the sequence again. After responding had stabilised, the rats were treated with a range of doses of a number of drugs. Impulsivity was assessed by several measures, including the mean chain length and the proportion of chains terminating in food delivery, and the distribution of chain lengths was analysed. The efficiency of the rats was similar under both FCN 8 and FCN 32, although it was more difficult to maintain a consistent baseline under FCN 32. Under the FCN 8 schedule, significant decreases in chain length were obtained with d-amphetamine (0.8–2.4 mg/kg), haloperidol (0.1 mg/kg), ethanol (1 and 3 g/kg) and chlordiazepoxide (10.0 mg/kg), and there were alterations in other measures consistent with an increase in impulsivity. Imipramine (1–10 mg/kg), citalopram (1–10 mg/kg) and metergoline (0.3–3.0 mg/kg) had no effect on mean chain length, although the first two drugs shifted the chain length distribution to the left. d-Amphetamine (0.4–1.2 mg/kg) and PCPA (100 mg/kg) reduced chain length and had other effects consistent with increased impulsivity under FCN 32 schedule, whereas imipramine had little, and citalopram no, effect. Taken generally, effect of the active drugs was relatively non-specific, including both a reduction in response rate and alterations in choice measures proposed to reflect an increase in impulsivity. Detailed analysis of the effect of amphetamine revealed that three processes were at work: chain shortening, an increased preference for the lever most closely associated with food delivery, and a gradual shift in the control over responding from the response sequence (pattern) to the individual lever press (act).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050673
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    The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain regions (1998)
    Springer
    Psychopharmacology 139 (1998), S. 95-107 
    Details
    ISSN: 1432-2072
    Keywords: Key words MK-801 ; Muscimol ; Discriminative stimulus ; Drug discrimination ; Ethanol ; GABAA ; NMDA ; Limbic system ; Nucleus accumbens ; Hippocampus ; Frontal cortex ; Amygdala ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study was conducted to assess the involvement of N-methyl-d-aspartate (NMDA) and γ-aminobutyric acid (GABA) receptor systems, located in specific limbic brain regions, in the discriminative stimulus effects of ethanol. Male Long-Evans rats were trained to discriminate between intraperitoneal (IP) injections of ethanol (1 g/kg) and saline on a two-lever drug discrimination task. The rats were then implanted with bilateral injector guides aimed at the nucleus accumbens core (AcbC), prelimbic cortex (PrLC), hippocampus area CA1 (CA1), or extended amygdala (i.e., at the border of the central and basolateral nuclei). Infusions of the non-competitive NMDA antagonist MK 801 in the AcbC or CA1 resulted in dose-dependent full substitution for IP ethanol. MK 801 infusion in the PrLC or amygdala failed to substitute for ethanol. Injection of the competitive NMDA antagonist CPP in the AcbC also failed to substitute for ethanol. Co-infusion of MK 801 in the hippocampus potentiated the effects of MK 801 in the AcbC, whereas NMDA infusion in the hippocampus attenuated the ability of MK 801 in the AcbC to substitute for ethanol. The direct GABAA agonist muscimol resulted in dose-dependent full substitution for IP ethanol when it was injected into the AcbC or amygdala, but failed to substitute when administered in the PrLC. Co-infusion of MK 801, but not CPP, potentiated the effects of muscimol in the AcbC. These results demonstrate that ethanol’s discriminative stimulus function is mediated centrally by NMDA and GABAA receptors located in specific limbic brain regions. The data also suggest that the discriminative stimulus effects of ethanol are mediated by interactions between ionotropic GABAA and NMDA receptors in the nucleus accumbens, and by interactions among brain regions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050694
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    Effects of third intracerebroventricular injections of corticotropin- releasing factor (CRF) on ethanol drinking and food intake (1998)
    Springer
    Psychopharmacology 139 (1998), S. 128-135 
    Details
    ISSN: 1432-2072
    Keywords: Key words Ethanol ; Alcohol ; Self-administration ; Drinking ; Drug intake ; Corticotropin-releasing hormone ; Corticotropin-releasing factor ; Rat ; Tension reduction hypothesis ; Food intake ; Body weight ; Stress ; Anxiety ; Tension ; ICV ; Third cerebral ventricle ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Corticotropin releasing factor (CRF), a neuropeptide secreted by hypothalamic and extrahypothalamic neurons, is thought to mediate stress-related behaviors. The tension reduction hypothesis suggests that ethanol drinking reduces stress; that drinking is reinforced by this reduced stress; and that the probability of drinking therefore subsequently increases. CRF also decrease food intake, and might decrease ethanol drinking similarly. We addressed these hypotheses directly by assessing the effects of intracerebroventricular (ICV) CRF upon ethanol drinking (1 h/day). Rats were provided drinking tubes containing ethanol solutions that were gradually incremented in concentration (from 2% to 8% w/v, over 38 days). Ethanol intakes remained stable, ranging from 0.4 to 0.5 g/kg per hour on average, and a two-bottle choice test revealed that ethanol was preferred reliably to water. Third-ICV cannulae were surgically implanted and CRF or vehicle was acutely injected immediately prior to the sessions. CRF dose-dependently reduced ethanol intake by 31% (0.5 µg) and 64% (5.0 µg), and reduced 24-h food by 9% and 21%, respectively, but did not alter body weights. ICV CRF reduced ethanol drinking despite any acute stress-like effects that may have been present. Hence, these data are inconsistent with the tension reduction hypothesis. On the other hand, our results support the concept that food intake and ethanol drinking may be mediated by similar mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050697
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    Effects of ethanol on Pavlovian autoshaping in rats (1998)
    Springer
    Psychopharmacology 139 (1998), S. 154-159 
    Details
    ISSN: 1432-2072
    Keywords: Key words Autoshaping ; Ethanol ; Pavlovian conditioning ; Lever-press ; Rat ; Learning ; Impulsivity ; Drug abuse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession IP injections of ethanol doses (0.00, 0.25, 0.50, 0.70, or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1–5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11–15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol’s effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession IP injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050700
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    Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and saccharin solutions in Fawn Hooded and Wistar rats (1998)
    Springer
    Psychopharmacology 139 (1998), S. 210-216 
    Details
    ISSN: 1432-2072
    Keywords: Key words Isolation-rearing ; Ethanol ; Sucrose ; Saccharin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Hooded rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050706
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    Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats (1998)
    Springer
    Psychopharmacology 135 (1998), S. 324-332 
    Details
    ISSN: 1432-2072
    Keywords: Key words Cannabinoid receptors ; Cocaine ; Food ; Incentive learning ; Morphine ; Rat ; Reward ; SR 141716 ; WIN 55212-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The involvement of cannabinoid processes in positive reinforcement was studied using an unbiased, one-compartment, conditioned place preference (CPP) procedure in rats. This was achieved by examining the ability of the selective antagonist of the CB1 cannabinoid receptor subtype, SR 141716, to counteract the CPP supported by classical reinforcers. The acquisition of CPP induced by cocaine (2 mg/kg), morphine (4 mg/kg) and food (standard chow and sucrose pellets) was dose-dependently blocked by pre-pairing administration of SR 141716 (0.03–3 mg/kg). However, SR 141716 (up to 10 mg/kg) did not significantly counteract the expression of cocaine-induced CPP. On the other hand, the synthetic CB receptor agonist, WIN 55212-2 (0.3–1 mg/kg), established a robust place aversion (CPA), as already described with other agonists, and CPP was never observed, even at 100-fold lower doses. The aversive effect of WIN 55212-2 was reversed by SR 141716 (0.3–1 mg/kg), suggesting that it was accounted for by the stimulation of CB1 receptors. These findings indicate that, on their own, CB receptor agonists are unable to generate the processes necessary to induce a pleasurable state in animals, as assessed in place conditioning procedures. Nevertheless, a cannabinoid link may be involved in the neurobiological events, allowing the perception of the rewarding value of various kinds of reinforcers. However, a permanent endogenous cannabinoid tone seems unlikely to be necessary to ensure the organism a basal hedonic level since, given alone, SR 141716 supported neither CPP nor CPA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050518
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    Corticotropin-releasing factor receptor blockade enhances conditioned aversive properties of cocaine in rats (1998)
    Springer
    Psychopharmacology 136 (1998), S. 247-255 
    Details
    ISSN: 1432-2072
    Keywords: Key words Corticotropin-releasing factor ; Cocaine ; Aversion ; Arousal ; Learning ; Runway ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral profile of corticotropin-releasing factor (CRF) in mediating anxiogenic-like and aversive responses to stressors may be particularly relevant for dependence and withdrawal in drug-experienced organisms. Moreover, stressful aspects of drug exposure in the drug naive organism may also induce CRF system activation. In the present studies, the dependence of aversive properties of cocaine on activation of endogenous CRF systems has been evaluated in rats using taste conditioning and runway self-administration paradigms. Systemic cocaine administration (20 mg/kg IP) produced a conditioned saccharin aversion which was dose-dependently potentiated by central administration of the CRF receptor antagonist, D-phe CRF (12–41). In addition, IV cocaine administration (0.75 mg/kg per injection IV) produced runway goal-box avoidance and conditioned place avoidance responses which were significantly accelerated by CRF antagonist treatment. In contrast, CRF receptor stimulation using CRF itself abolished cocaine-induced increases in goal latency in the runway paradigm. This generalized involvement of CRF systems in cocaine-related motivational/associative states is consistent with the comprehensive role of CRF in mediating emotional responses to non-drug stressors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050563
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    “Depression” increases “craving” for sweet rewards in animal and human models of depression and craving (1998)
    Springer
    Psychopharmacology 136 (1998), S. 272-283 
    Details
    ISSN: 1432-2072
    Keywords: Key words Depression ; Musical mood induction ; Chronic mild stress ; Progressive ratio schedule ; Sweet reward ; Craving ; Rat ; Human volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study consisted of two experiments, one in rats and one in human volunteers, that used the identical progressive ratio (PR) operant procedure. In both experiments, responding was reinforced under a progressively increasing work requirement, and different groups of subjects received reinforcers that varied in sweetness. In experiment 1, rats were subjected to chronic mild stress, a well-validated animal model of depression. Performance under the PR schedule increased in subjects reinforced with conventional precision pellets (which contain 10% sucrose) or very sweet pellets, but not in subjects reinforced with sugar-free pellets. In experiment 2, volunteers were subjected to a depressive musical mood induction. Performance under the PR schedule increased in subjects reinforced with chocolate buttons, but not in subjects reinforced with with buttons made from the relatively unpalatable chocolate substitute carob. In experiment 2, depressive mood induction also increased chocolate craving, as measured by a novel questionnaire, and there were significant correlations between chocolate craving and chocolate-reinforced PR performance. These results suggest that performance under the PR schedule provides a measure of craving rather than reward, and that craving for sweet rewards is increased by depressive mood induction in both animal and human models. Implications for the interpretation of pharmacological studies using the PR procedure are also discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050566
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    A comparison of the effects of clonidine and CNQX infusion into the locus coeruleus and the amygdala on naloxone-precipitated opiate withdrawal in the rat (1998)
    Springer
    Psychopharmacology 138 (1998), S. 133-142 
    Details
    ISSN: 1432-2072
    Keywords: Key words Clonidine ; ST-91 ; CNQX ; LC ; Amygdala ; Intracerebral infusion ; Withdrawal ; Naloxone ; Morphine ; Opioid ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Both the locus coeruleus (LC) and the amygdala have been implicated in aspects of opiate dependence and withdrawal. The LC is known to be one of the most sensitive sites for precipitating withdrawal behaviors after local opiate antagonist infusions in morphine-dependent subjects. The amygdala is also known to mediate antagonist-induced withdrawal behaviors and aversive motivational states. The goal of the present study was to evaluate directly the ability of noradrenergic agonists and glutamatergic antagonists to attenuate naloxone-precipitated withdrawal behaviors when infused into the LC or the central nucleus of the amygdala (CeA). The alpha-2-noradrenergic agonists clonidine or ST-91 were infused into the CeA to compare the effects of noradrenergic activation in the CeA to the attenuation of withdrawal previously observed in rats infused with clonidine into the LC, since the LC and CeA are known to contain co-localized opiate and noradrenergic receptors. The effects of microinfusions of the non-NMDA excitatory amino acid antagonist 6-cyano-2,3-dihydroxy-7-nitroquinoxaline (CNQX) were also infused into the LC and CeA since opiate withdrawal is associated with increased glutamatergic transmission. Intra-CeA clonidine or ST-91 (2.4 µg/0.5 µl or 1.0 µl) produced significant reductions primarily in the occurrence of irritability. Conversely, intra-CeA or intra-LC infusions of CNQX (2.5 µg/0.5 µl) significantly attenuated naloxone-precipitated withdrawal, an effect similar to the attenuation previously observed after intra-LC clonidine infusions. These data demonstrate the specific behavioral effects of altering glutamatergic and noradrenergic neurotransmission in the LC or CeA during naloxone-precipitated opiate withdrawal. Elucidation of the neuroanatomical circuitry involved in opiate withdrawal should increase our understanding of the neuroadaptations associated with drug dependence and subsequent withdrawal behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050655
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    Evidence for early opioid modulation of licking responses to sucrose and Intralipid: a microstructural analysis in the rat (1998)
    Springer
    Psychopharmacology 139 (1998), S. 342-355 
    Details
    ISSN: 1432-2072
    Keywords: Key words Mu-opioid ; Kappa-opioid ; Licking behaviour ; Bout structure ; Incentive salience ; Palatability ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioural mechanisms underlying the effects of the opioid antagonist naloxone (0.3–3 mg/kg IP), and the opioid agonists morphine (0.3–3 mg/kg SC), and U-50, 488H (0.3–3 mg/kg SC) on ingestive behaviour were investigated using a microstructural analysis of licking patterns for sucrose solutions and Intralipid (fat emulsions) in a brief contact test. Naloxone dose-dependently decreased the total number of licks and the number of bouts for sucrose and Intralipid, but did not affect mean bout duration. Morphine dose-dependently increased the total number of licks and the number of bouts for both test fluids. For Intralipid but not for sucrose drinking, morphine actually decreased mean bout duration. U-50, 488H significantly affected total licks, although the dose-effect relationship showed an inverted U-shaped function. There was a dose-dependent increase in mean bout duration following administration of U-50, 488H and an increase in bout number, although only the lowest dose differed significantly from the control condition. The results show that microstructural analysis can distinguish between the effects of naloxone, morphine and U-50, 488H on licking behaviour and indicate that selective opioid receptor subtypes may be differentially involved in ingestive processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050725
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    Effects of μ and δ opioid agonists and antagonists on affective vocal and reflexive pain responses during social stress in rats (1998)
    Springer
    Psychopharmacology 139 (1998), S. 364-375 
    Details
    ISSN: 1432-2072
    Keywords: Key words Affect ; Aggression ; Antinociception ; Opioids ; Rat ; Stress ; Vocalization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present experiments evaluated the influence of intraventricular μ and δ opioid receptors on affective vocal and reflexive responses to aversive stimuli in socially inexperienced, as well as defensive and submissive responses in defeated, adult male Long-Evans rats. Defeat stress consisted of: (1) an aggressive confrontation in which the experimental intruder rat exhibited escape, defensive and submissive behaviors [i.e., upright, supine postures and ultrasonic vocalizations (USV)], and subsequently, (2) protection from the resident stimulus rat with a wire mesh screen for 10–20 min. Defeat stress was immediately followed by an experimental session with tactile startle (20 psi). The μ opioid receptor agonists morphine (0.1–0.6 μg ICV) and [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin (DAMGO; 0.01–0.3 μg ICV), and the δ opioid receptor agonist [D-Pen2,5]-enkephalin (DPDPE; 10–100 μg ICV) dose-dependently decreased startle-induced USV and increased tail-flick latencies in socially inexperienced and defeated rats. Of greater interest, morphine, DAMGO and DPDPE increased the occurrence of the submissive crouch posture, and defeated rats were more sensitive than socially inexperienced rats to the startle-induced USV-suppressive and antinociceptive effects of morphine and DPDPE. The antinociceptive effects of DAMGO were likewise obtained at lower doses in defeated rats. Finally, the USV-suppressive effects of morphine and DAMGO were reversed with the μ receptor antagonist naltrexone (0.1 mg/kg IP), but the USV-suppressive effects produced by DPDPE were not reversed with the δ receptor antagonist naltrindole (1 mg/kg IP). These results confirm μ, but not δ opioid receptor activation as significant in affective vocal, passive-submissive behavior, as well as reflexive antinociception. Furthermore, similar to previous studies with restraint and electric shock stress, the facilitation of μ opioid effects on vocal responses and antinociception is consistent with the proposal that defeat stress activated endogenous opioid mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050727
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    Distribution after repeated oral administration of different dose levels of risperidone and 9-hydroxy-risperidone in the brain and other tissues of rat (1998)
    Springer
    Psychopharmacology 139 (1998), S. 356-363 
    Details
    ISSN: 1432-2072
    Keywords: Key words Risperidone ; 9-Hydroxy-risperidone ; Antipsychotics ; Tissue distribution ; Regional brain distribution ; Brain to plasma level ratio ; Dose-tissue level relationship ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were treated with daily oral doses of 1, 4, and 6 mg/kg risperidone (RSP) and its metabolite, 9-hydroxy-risperidone (9-OH-RSP), for 15 consecutive days. Concentrations of RSP and 9-OH-RSP were measured in plasma, brain, liver, kidney, lungs and fat tissue by high-performance liquid chromatography with electrochemical detection. Non-specific distribution of RSP and 9-OH-RSP in various brain regions was also studied after administration of 6 mg/kg per day oral dose for 15 days. After RSP treatment, concentrations of 9-OH-RSP were higher than those of RSP in plasma and tissues except in brain, where both compounds were present in nearly equal concentrations. Similarly, after 9-OH-RSP treatment, levels of 9-OH-RSP were higher than levels of either RSP or 9-OH-RSP or the sum of RSP and 9-OH-RSP levels measured after treatment with RSP. There was a moderate relationship between RSP dose and tissue levels of RSP and 9-OH-RSP (all r s ≥ 0.62, P 〈 0.01), except in fat. There was also a strong relationship between the dose and tissue levels of 9-OH-RSP (all r s≥ 0.68, P 〈 0.005). A significant relationship was found between plasma levels of RSP and brain levels of RSP and 9-OH-RSP (all r s ≥ 0.57, P 〈 0.03) after treatment with RSP. After 9-OH-RSP treatment, a much stronger relationship was observed between plasma and brain 9-OH-RSP levels (r s ≥ 0.90, P 〈 0.005). The plasma concentrations of RSP and 9-OH-RSP appear to reflect their concentrations in brain. The tissue-to-plasma ratios of RSP and 9-OH-RSP were relatively low compared to other antipsychotics. In liver, kidney and lung the tissue to plasma ratio for RSP and 9-OH-RSP after treating with RSP ranged from 0.85 to 3.4. The brain to plasma ratio for RSP and 9-OH-RSP was several-fold lower than that in peripheral tissues. After RSP administration, the mean brain to plasma level ratio for RSP was 0.22, and for 9-OH-RSP to it was 0.04. The brain to plasma ratio of 9-OH-RSP after giving 9-OH-RSP was similarly low (0.04). The low brain/plasma ratio of high potency RSP and 9-OH-RSP may in part be due to their low lipophilicity, log P = 3.04 and 2.32, respectively, resulting in limited non-specific accumulation in brain tissue.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050726
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    Ethanol induces impulsive-like responding in a delay-of-reward operant choice procedure: impulsivity predicts autoshaping (1998)
    Springer
    Psychopharmacology 139 (1998), S. 376-382 
    Details
    ISSN: 1432-2072
    Keywords: Key words Autoshaping ; Delay-of-reward ; Impulsivity ; Ethanol ; Sensitivity ; Individual differences ; Drug abuse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Autoshaping conditioned responses (CRs) are reflexive and targeted motor responses expressed as a result of experience with reward. To evaluate the hypothesis that autoshaping may be a form of impulsive responding, within-subjects correlations between performance on autoshaping and impulsivity tasks were assessed in 15 Long-Evans hooded rats. Autoshaping procedures [insertion of retractable lever conditioned stimulus (CS) followed by the response-independent delivery of food (US)] were followed by testing for impulsive-like responding in a two-choice lever-press operant delay-of-reward procedure (immediate small food reward versus delayed large food reward). Delay-of-reward functions revealed two distinct subject populations. Subjects in the Sensitive group (n=7) were more impulsive-like, increasing immediate reward choices at longer delays for large reward, while those in the Insensitive group (n=8) responded predominantly on only one lever. During the prior autoshaping phase, the Sensitive group had performed more autoshaping CRs, and correlations revealed that impulsive subjects acquired the autoshaping CR in fewer trials. In the Sensitive group, acute injections of ethanol (0, 0.25, 0.50, 1.00, 1.50 g/kg) given immediately before delay-of-reward sessions yielded an inverted U-shaped dose-response curve with increased impulsivity induced by the 0.25, 0.50, and 1.00 g/kg doses of ethanol, while choice strategy of the Insensitive group was not influenced by ethanol dose. Ethanol induced impulsive-like responding only in rats that were flexible in their response strategy (Sensitive group), and this group also performed more autoshaping CRs. Data support the hypothesis that autoshaping and impulsivity are linked.
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    URL: http://dx.doi.org/10.1007/s002130050728
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    The effects of 5-HT1A receptor agonists, 5-HT1A receptor antagonists and their interaction on the fear-potentiated startle response (1998)
    Springer
    Psychopharmacology 139 (1998), S. 383-390 
    Details
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Fear-potentiated startle response ; 8-OH-DPAT ; Flesinoxan ; WAY 100 ; 635 ; (±)-Pindolol ; DU 125 ; 530 ; Lower lip retraction ; 5-HT1A receptor agonist ; 5-HT1A receptor antagonist ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present study investigated whether the anxiolytic effect of 5-HT1A receptor agonists on the fear-potentiated startle response could be antagonized by 5-HT1A receptor antagonists. Therefore, control and fear-potentiated startle amplitudes were measured after co-administration of vehicle, flesinoxan (10 mg/kg PO) or 8-OH-DPAT (0.3 mg/kg SC) and DU 125,530 (0, 1, 3 and 10 mg/kg SC), (±)-pindolol (0, 3, 10 and 30 mg/kg SC) or WAY 100,635 (0, 0.1, 0.3 and 1 mg/kg SC). Unexpectedly, the three antagonists themselves as measured in the vehicle-pretreatment groups dose-dependently decreased startle potentiation. Further, DU 125,530 and WAY 100,635 were able to reverse the attenuating effect of 8-OH-DPAT, while no antagonism of the flesinoxan effect on startle potentiation was found. In contrast, both the flesinoxan- and 8-OH-DPAT-induced lower lip retraction were antagonized by DU 125,530 and WAY 100,635, but not by (±)-pindolol. The findings of the present study suggest that drugs acting on 5-HT1A receptors differentially affect lower lip retraction and startle potentiation probably mediated by different neuronal populations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050729
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    Repeated administration of amphetamine induces sensitisation to its disruptive effect on prepulse inhibition in the rat (1998)
    Springer
    Psychopharmacology 135 (1998), S. 401-406 
    Details
    ISSN: 1432-2072
    Keywords: Key words Acoustic startle response ; Prepulse inhibition ; Schizophrenia ; Sensitisation ; Amphetamine ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Male Sprague-Dawley rats were repeatedly treated with amphetamine (AMP, 1 mg/kg, SC) at 3- day intervals for 15 days and tested for prepulse inhibition of acoustic startle after each treatment. This treatment regimen induced sensitisation in the animals as evidenced by a progressive increase in the disruptive effect of AMP on prepulse inhibition. Persistent changes in brain function was indicated, since an increase in disruptive effect was observed in sensitised animals also after a 22-day-long drug- and test-free period. The development of sensitisation was blocked by pretreatment with haloperidol (HPD, 0.1 mg/kg, SC), which suggests that sensitisation to the disruptive effect of AMP was dependent on dopamine (DA) D2 receptor activation. Furthermore, the development of sensitisation was blocked by adrenalectomy, which suggests that sensitisation was dependent also on circulating adrenal hormones. Increased DA-ergic activity has been implicated in the pathophysiology of schizophrenia and AMP-induced sensitisation to the neuronal functions that modulate prepulse inhibition may be an experimental model to investigate this hypothesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050528
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    Motivational effects of compounding discriminative stimuli associated with food and cocaine (1998)
    Springer
    Psychopharmacology 136 (1998), S. 70-74 
    Details
    ISSN: 1432-2072
    Keywords: Key words Self-administration ; Stimulus control ; Incentive-motivation ; Stimulus compounding ; Cocaine ; Food ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In previous experiments, the compounding of two discriminative stimuli associated with the same reinforcer increased rats’ responding approximately three-fold, regardless of whether the reinforcer was food, water, cocaine, or shock-avoidance. Compounding a discriminative stimulus associated with food with one associated with water increased responding two-fold. In the present experiment, compounding a discriminative stimulus associated with food with one associated with cocaine increased responding two-fold. These results support the hypothesis that 1) the effects of stimuli associated with reinforcers from the same incentive class (appetitive or aversive) are mutually enhancing, and 2) the combined effects of stimuli associated with two different reinforcers from within the same class are not as strong as those of two stimuli associated with the same reinforcer. These results also suggest that discriminative stimuli associated with non-drug reinforcers may increase the motivation to self-administer cocaine when encountered in combination with drug-related stimuli.
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    URL: http://dx.doi.org/10.1007/s002130050540
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    Anxiolytic activity of ginkgolic acid conjugates from Indian Ginkgo biloba (1998)
    Springer
    Psychopharmacology 136 (1998), S. 148-152 
    Details
    ISSN: 1432-2072
    Keywords: Key words Indian Ginkgo biloba (IGb) ; Ginkgolic acid conjugates ; EGb 761 ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ginkgolic acid conjugates (GAC) (6-alkylsalicylates, namely n-tridecyl-, n-pentadecyl-, n-hepta- decyl-, n-pentadecenyl- and n-heptadecenylsalicylates) isolated from the leaves of Indian Ginkgo biloba Linn., (IGb) were tested for their putative role in anxiety in rats. Elevated plus maze, open-field behaviour, novelty-induced feeding latency and social interaction were the rodent behavioural models used in this study. GAC (0.3 and 0.6 mg/kg, each, PO) on single acute administration, showed dose-related changes in the behaviour. GAC (0.6 mg/kg) and DZ augmented open arm entries, the open arm/closed arm entries ratio and increased time spent in the open arm on the elevated plus maze. In the open field, GAC (0.6 mg/kg) and DZ significantly increased ambulation and reduced the immobility time. EGb 761 showed a similar profile. GAC (0.6 mg/kg) and DZ significantly attenuated the increased latency to feed in novel environment. By contrast, EGb 761 and Ginkocer further augmented feeding latency. None of the drugs tested showed any significant effect in the social interaction test. GAC showed consistent and significant anxiolytic activity in all the variables investigated. By contrast, EGb 761 and Ginkocer, which are devoid of GAC, did not evoke significant activity. However, increased rearing and decreased immobility time only in open field behaviour shown by EGb 761 may be due to some antianxiety activity of a lesser degree. Our observations suggest that GAC may be the active constituents of Ginkgo biloba responsible for the anxiolytic activity.
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    URL: http://dx.doi.org/10.1007/s002130050550
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    Buprenorphine alters ethanol self-administration in rats: dose-response and time-dependent effects (1998)
    Springer
    Psychopharmacology 140 (1998), S. 29-37 
    Details
    ISSN: 1432-2072
    Keywords: Key words Buprenorphine ; Opioids ; Ethanol ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Buprenorphine is a partial opioid agonist derived from thebaine and has high affinity for μ and κ opioid receptors. The present study investigated dose-response (0.03, 0.15, 0.3, 3 mg/kg) and time-dependent effects of buprenorphine (1.5 or 4 h post-treatment) on EtOH self-administration in outbred Sprague-Dawley rats. Freely feeding and drinking rats were trained to initiate EtOH self-administration for 1 h daily using the ascending concentration procedure, wherein they were provided with increasing concentrations of EtOH at 2, 5, 7, 9 and 11% (v/v), respectively. Water was concurrently available with each concentration. Animals were maintained on a given concentration of EtOH for 5 days. By day 21, animals began their stabilization on the 11% regimen and remained on this concentration throughout the remainder of the study. EtOH and water consumption were recorded daily at both 10- and 60-min intervals. At 1.5 h post-buprenorphine, all test doses greatly suppressed both EtOH and water intake at the 10-min interval. At the 60-min interval, all but the lowest dose (0.03 mg/kg) significantly suppressed EtOH intake, while only the highest dose (3 mg/kg) suppressed water intake. In contrast to the suppressant profile observed at 1.5 h post-buprenorphine, at 4 h post-buprenorphine the lower doses (0.03 and 0.15 mg/kg) significantly increased EtOH intake while the higher doses (0.3 and 3 mg/kg) continued to suppress intake. None of the doses of buprenorphine altered water intake 4 h post-buprenorphine. The results support previous research demonstrating the utility of low doses of buprenorphine in suppressing behavior rewarded by a non-opioid drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050735
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    The influence of environment on the induction of sensitization to the psychomotor activating effects of intravenous cocaine in rats is dose-dependent (1998)
    Springer
    Psychopharmacology 137 (1998), S. 90-98 
    Details
    ISSN: 1432-2072
    Keywords: Key words Environment ; Associative learning ; Stress ; Rotational behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The acute psychomotor response and development of sensitization to amphetamine is attenuated if IP injections are given in the cage where a rat lives relative to when injections are given in a novel but physically identical test environment. Furthermore, when the environmental cues predicting IP injections are completely eliminated by using remotely activated IV injections in the home cage, 1.0 mg/kg amphetamine produces a very small acute response and no sensitization. The same treatments do produce sensitization if IV injections are signaled by placement of the rat in a novel test cage. The present experiment was designed to determine if there is a similar effect of environmental condition on the response to IV cocaine, and to what extent the effect may be dose-dependent. This was accomplished by comparing the psychomotor activating effects (rotational behavior) of repeated IV administrations of one of eight doses of cocaine (0.0, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 7.2 mg/kg) given in the home cage, with infusions of the same doses given in a novel test cage. There was no effect of environment on the acute psychomotor response to cocaine. There was, however, a significant effect of environment on the induction of sensitization. A higher dose of cocaine was required to induce sensitization when IV administrations were given in the home cage than when they were given in a physically identical but novel test environment. At high doses, however, cocaine induced sensitization regardless of environmental condition. The results suggest that the effect of this environmental manipulation is to shift the dose-effect curve for the induction of sensitization, and support the notion that the ability of psychostimulant drugs to induce sensitization can be modulated by the circumstances surrounding drug administration.
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    URL: http://dx.doi.org/10.1007/s002130050597
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    Evidence for a functional interaction between 5-HT1A and 5-HT2 receptors in rats (1998)
    Springer
    Psychopharmacology 140 (1998), S. 69-74 
    Details
    ISSN: 1432-2072
    Keywords: Key words 8-OH-DPAT ; DOI ; Isobologram ; 5-HT1A/2 interaction ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Evidence of a functional interaction between serotonin 5-HT1A and 5-HT2 receptor subtypes has been compromised by incomplete experimental designs and conflicting data. To test for such an interaction, combinations of the 5-HT1A agonist 8-OH-DPAT and the 5-HT2 agonist DOI were administered to rats prior to testing of locomotor activity in the Behavioral Pattern Monitor (BPM). The BPM is an activity and holeboard chamber that enables analyses of quantitative and qualitative changes in locomotor and investigatory activity. Dose-response studies of 8-OH-DPAT and DOI alone and in the presence of selected doses of the other drug were performed in order to allow isobolographic analysis, which characterizes the relationship of two drugs as either additive (no interaction), supra-additive, or infra-additive. Rats treated with saline, 8-OH-DPAT (6.25, 12.5, 25, or 50 μg/kg SC), DOI (0.15, 0.3, or 0.6 mg/kg SC), or selected combinations of both drugs were tested in the BPM for 1 h. Isobolographic analysis of the effects on locomotor activity revealed that 8-OH-DPAT and DOI interact in an infra-additive manner. Thus, at a functional level, 5-HT1A and 5-HT2 receptors interact antagonistically in the modulation of locomotor activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050740
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    Discriminative stimulus effects of S(−)–methcathinone (CAT): a potent stimulant drug of abuse (1998)
    Springer
    Psychopharmacology 140 (1998), S. 250-256 
    Details
    ISSN: 1432-2072
    Keywords: Key words Methcathinone ; Drug discrimination ; Stimulants ; Fenfluramine ; Haloperidol ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methcathinone (“CAT”) is a CNS stimulant that is a very significant drug of abuse in the former Soviet Union. It has also appeared on the clandestine market in the United States and has been recently classified as a Schedule I substance. In the present study, S(−)-methcathinone [S(−)-CAT, 0.50 mg/kg, IP] was employed as the training drug in a two-lever drug discrimination task in rats. Once established, the S(−)-CAT stimulus was shown to have a rapid onset to action (within 5 min) and a duration of effect of approximately 60–90 min. In tests of stimulus generalization (substitution), the S(−)-CAT (ED50 = 0.11 mg/kg) stimulus generalized to S(+)-methamphetamine (ED50 = 0.17 mg/kg), S(−)-cathinone (ED50 =  0.19 mg/kg), S(+)-amphetamine (ED50 = 0.23 mg/kg), aminorex (ED50 = 0.27 mg/kg), (±)-CAT (ED50 = 0.25 mg/kg), (±)-cathinone (ED50 = 0.41 mg/kg), R(+)-CAT (ED50 = 0.43 mg/kg), cis-4-methylaminorex (ED50 = 0.49 mg/kg), methylphenidate (ED50 = 0.83 mg/kg), and cocaine (ED50 = 1.47 mg/kg). S(−)-CAT-stimulus generalization did not occur to fenfluramine, a structurally related nonstimulant anorectic. Lastly, haloperidol (AD50 = 0.18 mg/kg), a dopamine receptor antagonist, potently antagonized the S(−)-CAT stimulus. It is concluded that S(−)-methcathinone is a very potent CNS stimulant, which appears to produce its stimulus effect, at least in part, via a dopaminergic mechanism.
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    URL: http://dx.doi.org/10.1007/s002130050765
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    Behavioral effects of nicotine, amphetamine and cocaine under a fixed-interval schedule of food reinforcement in rats chronically exposed to caffeine (1998)
    Springer
    Psychopharmacology 140 (1998), S. 257-271 
    Details
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Amphetamine ; Cocaine ; Caffeine ; Drug interaction ; Schedule-controlled behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Epidemiological surveys demonstrate that caffeine, the main psychoactive ingredient of coffee, is a positive correlate in drug abuse. To characterize the behavioral nature of caffeine interactions with other psychomotor stimulants, we examined the effects of chronic caffeine exposure on the behavioral responses to nicotine, amphetamine, cocaine, the selective D1 agonist SKF-82958 and the selective D2 receptor agonist NPA, in rats responding under a fixed interval (FI) schedule of food reinforcement. Following stabilization of rates and temporal patterns of responding (mathematically expressed as quarter-life values, QL), twenty-one Sprague-Dawley rats responding under a 5-min FI schedule of food reinforcement were divided into two groups; one (twelve rats) maintained on tap water (control) and the other (nine rats) on caffeine (3 mg/ml added to the drinking water). Following the substitution of caffeine solution for tap water, behavior was temporarily disrupted as evidenced by decreases in responding and QL values which reached a maximum after 72 h (rate 60% and QL 30% below baseline levels). Rats developed complete tolerance to these effects of caffeine over 5 days of caffeine exposure. After response rate and QL values stabilized, effects of drugs were evaluated. Nicotine (0.01–1.0 mg/kg; SC), amphetamine (0.1–5.6; IP), and cocaine (1.0–17; IP) each produced biphasic dose-dependent changes in response rate with maximum increases in response rate following intermediate doses and decreases in response rates following higher doses. The increase in rates of responding produced by amphetamine or cocaine (but not nicotine) were greater (P〈0.05) in caffeine-drinking than in water-drinking rats. Both SKF-82958 (0.001–0.3 mg/kg; IP) and NPA (0.0001–0.1; IP) produced only dose-dependent decreases in rates of responding. Caffeine-drinking rats were less sensitive to the rate-depressant effects of SKF-82958 (P〈0.05) than water-drinking rats. However, similar changes (P〉0.05) were produced by NPA in both groups. Except for amphetamine, the remaining drugs produced similar (P〉0.05) dose-dependent decreases in QL values in water- and caffeine-drinking rats. Amphetamine produced smaller decreases in QL values in caffeine-drinking rats than in water-drinking rats (P〈0.05). Chronic exposure to caffeine produced complete insurmountable tolerance to the response-rate increasing (stimulant) effects of acute caffeine (3.0–17 mg/kg; IP) in caffeine-drinking rats. In conclusion, our study revealed that chronic caffeine exposure potentiates the behavioral response to amphetamine and cocaine but not to that of nicotine in rats responding under a FI schedule of food reinforcement. Thus, it is likely that these effects are mediated through different pharmacological mechanisms.
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    URL: http://dx.doi.org/10.1007/s002130050766
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    The pharmacology of impulsive behaviour in rats IV: the effects of selective serotonergic agents on a paced fixed consecutive number schedule (1998)
    Springer
    Psychopharmacology 140 (1998), S. 319-330 
    Details
    ISSN: 1432-2072
    Keywords: Key words Impulsivity ; Rat ; Serotonin agonist ; Serotonin antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An impulsive cognitive style may affect behaviour in several different ways, including rapid decision making, intolerance of the delay of reward and a tendency to terminate chains of responses prematurely. It has been proposed to measure the last of these in rats using fixed consecutive number (FCN) schedules. The present study uses a modified version of the FCN procedure in which responding was paced by retracting the response lever for short periods between presses. In this way, the experimenter can control the maximum rate of responding. The procedure was made up of two components. In both, the schedule requirement was FCN 8, but in the Fast component lever presses were spaced by a minimum of 2.5 s and in the Slow component by a minimum of 5 s. Alterations in impulsivity were inferred from changes in the mean chain length and the distribution of chain lengths. The 5-HT1A agonist, 8-OH-DPAT (0.03–0.3 mg/kg), increased chain lengths within a narrow dose range, whereas the 5-HT1A antagonist, WAY 100 635 (0.03–0.3 mg/kg), reduced chain lengths. The 5-HT2 agonist, DOI (0.1–1.0 mg/kg), markedly reduced chain lengths, whereas the 5-HT2 antagonist, ritanserin (0.03–0.3 mg/kg), had no effect. The 5-HT1A/1b agonist, RU 24969 (0.03–0.3 mg/kg), reduced chain lengths. The 5-HT releaser, p-chloramphetamine (0.1–1.0 mg/kg), had a weak, biphasic effect, slightly reducing the number of short chains at the lowest dose tested and slightly increasing this number at the highest dose. Other drugs tested, citalopram (1.0–10.0 mg/kg), metergoline (0.3–3.0 mg/kg) and MDL-72222 (0.1–3.0 mg/kg), had no significant effects. These results suggest that stimulation of 5-HT1A receptors reduces impulsivity, whereas stimulation of 5-HT2 receptors increases it. These data are in agreement with previous results using the DRL-72 schedule, and indicate that there is no simple role for serotonin in the control of impulsivity.
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    URL: http://dx.doi.org/10.1007/s002130050773
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    The effects of dopamine D3/D2 receptor agonists on intracranial self stimulation in the rat (1998)
    Springer
    Psychopharmacology 140 (1998), S. 405-410 
    Details
    ISSN: 1432-2072
    Keywords: Key words Intracranial self-stimulation ; Quinelorane ; Quinpirole ; (±)7-OH-DPAT ; Lateral hypothalamus ; Rat ; Reward
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the dopamine D3/D2 receptor agonists quinpirole, quinelorane and (±)7-OH-DPAT [(±) 7-hydroxy-2(N,N-di-n-propylamino) tetralin] on intracranial self-stimulation (ICSS) were investigated. Rats implanted with bipolar electrodes into the lateral hypothalamus were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. Three measures of responding were calculated; the frequency at which responding was 50% of the maximum (M50), the asymptotic response rate and the total area under the curve (AUC) for each frequency sweep. Quinpirole (2.2–66.0 μg/kg SC) significantly increased M50 and reduced both asymptote and AUC. Quinelorane (0.25–79.0 μg/kg SC) had no significant effect on M50 values but significantly reduced both asymptote and AUC. (±)7-OH-DPAT (2.5–74.0 μg/kg) did not significantly affect any of the measures. The data show that low doses of quinpirole and quinelorane, but not (±)7–OH–DPAT, inhibit ICSS maintained by electrodes in the lateral hypothalamus. Either dopamine D2 or dopamine D3 receptor stimulation may play a role in mediating ICSS inhibition, but studies with more selective receptor agonists and antagonists are required to define the role of each receptor.
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    URL: http://dx.doi.org/10.1007/s002130050782
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    The distribution of intramural nerves in urinary bladder after partial denervation in the female rat (1998)
    Springer
    Urological research 26 (1998), S. 291-297 
    Details
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Rat ; Pelvic ganglion ; Innervation ; Denervation ; Plasticity ; Age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the degree of neuronal plasticity following a partial denervation of the rat urinary bladder. Using acetylcholinesterase staining we found that the postganglionic nerves from the pelvic ganglion reach the intact bladder as 1–4 nerve trunks on each side, slightly ventral and caudal to the ureteral orifices. Normally a few thinner nerves also reach the bladder posterolateral to the ureterovesical junction. The nerves ventral to the ureters run in the ventral longitudinal muscle layer as well-defined trunks with a pattern that does not differ much from one animal to another. The nerves reaching the bladder dorsolaterally innervate the dorsolateral aspects in a more irregular fashion. Some anastomoses are found across the midline between nerves from either side. This nerve pattern is already in place in newborn rats. After removal of the pelvic ganglion on one side in the adult rat the ipsilateral ventral nerves rapidly degenerate, whereas some dorsolateral␣nerves usually survive. Axons from the intact ventral␣nerves can be seen crossing over to the denervated side in the anastomoses. After 13 weeks the surviving ventral nerves, which normally run at some distance from the ventral midline, now run in the midline with equal amounts of ventral longitudinal muscle on either side, and with their branches evenly distributed to both sides. The same pattern is seen after 27 weeks. Unilateral ganglionectomy in 3-week-old rats leads to the same changes in nerve distribution as in the adult rat. We conclude that there is a high degree of plasticity in the bladder innervation following a partial denervation, and that this plasticity includes the distribution of its main intramural nerve trunks.
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    URL: http://dx.doi.org/10.1007/s002400050060
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    Cystometrical evaluation of acute and chronic overdistension in the rat urinary bladder (1998)
    Springer
    Urological research 26 (1998), S. 325-330 
    Details
    ISSN: 1434-0879
    Keywords: Key words Urinary bladder ; Obstruction ; Hypertrophy ; Cystometry ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The urodynamic effects of an experimental, partial infravesical outlet obstruction in rats were studied and compared with the effects in sham-operated controls, and in animals that had undergone 24 h of total outlet obstruction. The animals were studied up to 42 days after surgery. Bladder weight increased with time in the partially obstructed group to reach a final value of 6 times that of the control. In water loading experiments micturition volume was unaffected by sham operation. In the partially obstructed bladders it decreased initially but normalized with time. In the group that had undergone 24 h of total obstruction micturition volume also decreased initially but then became significantly higher than in the controls. In cystometry experiments the partially obstructed bladders developed a considerable residual urine and increased threshold and micturition pressures. Detrusor instability was present already after 10 days. Also in the cystometry experiments the bladders that had been totally obstructed for 24 h had increased micturition volumes. Residual volume was only slightly affected by atropine in the control and partially obstructed bladders but increased 7-fold in rats in which the bladder had been totally obstructed for 24 h 42 days previously. We conclude that there is a close relationship between bladder weight, residual volume and micturition pressure in the partially obstructed bladder, and that 24 h of total obstruction results in disturbances of bladder function that might be related to denervation phenomena previously reported by others.
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    URL: http://dx.doi.org/10.1007/s002400050064
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    Effects of smoking on testicular function and fertilizing potential in rats (1998)
    Springer
    Urological research 26 (1998), S. 45-48 
    Details
    ISSN: 1434-0879
    Keywords: Key words Testicular function ; Smoking ; Fertility ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We evaluated the effects of smoking on testicular function and fertilizing potential in rats. Twenty rats (group A) were exposed to the smoke of 20 cigarettes for 1 h per day. Ten rats (group B) were exposed to the smoke of 40 incense sticks for 1 h per day, and an additional 10 rats served as a control group (group C). After 10 weeks of daily exposure, serum levels of nicotine and cotinine were assessed, and a mating test was conducted. Five days later, serum concentrations of testosterone before and after human chorionic gonadotropin (hCG) stimulation, gonadotropins, and epididymal sperm content and motility were evaluated. In addition, in vitro fertilization was carried out. Nicotine and cotinine were detected in group A, but not in groups B and C. Basal serum testosterone and gonadotropin concentrations did not differ significantly among the three groups, but the testosterone response to hCG stimulation was significantly lower in group A than in groups B and C. Group A showed significant reductions in epididymal sperm content and motility, and in fertility in vivo and in vitro. These findings suggest that smoking leads to a secretory dysfunction of the Leydig cells, and also a deficiency in sperm maturation and spermatogenesis. In addition, smoking has a detrimental effect on sperm fertilizing potentials in vivo and in vitro.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002400050022
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