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  • 101
    Electronic Resource
    Electronic Resource
    NOS-like immunoreactive neurons express GABA-like immunoreactivity in rabbit and rat retinae (1998)
    Springer
    Experimental brain research 120 (1998), S. 109-113 
    Details
    ISSN: 1432-1106
    Keywords: Key words Nitric oxide synthase ; GABA ; Retina ; Rabbit ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In rabbit and rat retinae, wholemounted preparations and 40 μm thick vibratome sections were processed for nitric oxide synthase (NOS) immunoreactivity and consecutive semithin sections were immunostained with anti-NOS and anti-GABA antisera, respectively. Two types of NOS-labelled amacrine cells were identified: type 1 cells with larger somata were intensely stained, and type 2 cells with smaller somata were weakly stained. A few displaced amacrine cells also showed NOS-like immunoreactivity. All these NOS-like immunoreactive neurons also expressed GABA-like immunoreactivity. Thus, nitric-oxide-containing neurons might constitute a subpopulation of GABAergic neurons in rabbit and rat retinae.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050383
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  • 102
    Electronic Resource
    Electronic Resource
    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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  • 103
    Electronic Resource
    Electronic Resource
    Group III metabotropic glutamate receptor agonists modulate high voltage-activated Ca2+ currents in pyramidal neurons of the adult rat (1998)
    Springer
    Experimental brain research 119 (1998), S. 237-244 
    Details
    ISSN: 1432-1106
    Keywords: Key words Calcium conductances ; l-2-Amino-4-phosphonobutyrate ; l-Serine-O-phosphate ; Neuroprotection ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In pyramidal neurons of the rat sensorimotor cortex, we have investigated the modulation of high voltage-activated calcium currents by agonists at group III metabotropic glutamate receptors (mGluRs). l-2-Amino-4-phosphonobutyrate (l-AP4) and l-serine-O-phosphate (l-SOP) reduced calcium currents in the vast majority of cells isolated from the adult animal. Interestingly, this modulation was negligible in the young animals (2–14 postnatal days), becoming prominent only after full development (more than 21 days). The efficacy of l-SOP mimicked l-AP4 in reducing calcium currents. Yet, l-SOP produced saturating responses at about 3 μM and significant modulation at nanomolar concentrations (EC50=923 nM). The voltage-dependence of the group III mGluR-mediated responses was evaluated by comparing the inhibition of “standard” and “facilitated” conductances. On the calcium currents facilitated by depolarizing prepulse, 3 μM l-SOP produced a mean 13.4% inhibition compared with 19.6% in control condition, supporting the proposition that part of the modulation was voltage-dependent. The calcium current inhibition caused by the activation of group III metabotropic glutamate receptors was only partially sensitive to ω-conotoxin GVIA, but largely inhibited by ω-agatoxin IVA, at concentrations (100 nM) known to block P- and Q-type channels. Conversely, the dihydropyridine antagonists nifedipine and nimodipine (50–500 nM) failed to prevent the group III mGluR-mediated response in the majority of tested cells (more than 65%). Furthermore, the long-lasting tail promoted by the inclusion of the dihydropyridine agonist Bay K 8644 was not consistently affected by l-SOP and l-AP4. These findings imply that the observed modulation involves different channel subtypes, namely N- and P- or Q-type channels, and suggests that group III mGluRs play an important role in the intrinsic and synaptic functions of adult cortical pyramidal neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002210050337
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  • 104
    Electronic Resource
    Electronic Resource
    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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  • 105
    Electronic Resource
    Electronic Resource
    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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  • 106
    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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  • 107
    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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  • 108
    Electronic Resource
    Electronic Resource
    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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  • 109
    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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  • 110
    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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  • 111
    Electronic Resource
    Electronic Resource
    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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  • 112
    Electronic Resource
    Electronic Resource
    Arsenobetaine is not a major metabolite of arsine gas in the rat (1998)
    Springer
    Archives of toxicology 72 (1998), S. 706-710 
    Details
    ISSN: 1432-0738
    Keywords: Keywords Arsine gas ; Metabolism ; Arsenobetaine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Many organisms can easily dispose of toxic inorganic arsenic species through gradual methylation of the element and further urinary excretion. In order to clarify the urinary excretion of arsenobetaine observed in a human case of intoxication by arsine, the capacity of highly methylated arsenical synthesis has been investigated in rats acutely exposed during 1 h to increasing concentrations of the same gas [4 to 80 mg AsH3/m3]. Urinary metabolites of arsenic were determined with good agreement in two (Belgian and Italian) laboratories using two different analytical procedures. The sum of inorganic, mono- and dimethylated metabolites of arsenic in urine was shown to be related to the intensity of exposure to arsine. A biphasic relationship was observed: 1 h exposure to 〉60 mg AsH3/m3 led to metabolite excretion which is roughly 10 times higher than for exposure levels below that limit, suggesting the saturation of a binding site reserve and the availability for metabolism of a greater proportion of the As absorbed above this threshold. Arsenobetaine production, if any, could only be detected when its presence in food was excluded; in addition, amounts appeared negligible and could be disregarded as a common arsenic metabolite in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050564
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  • 113
    Electronic Resource
    Electronic Resource
    Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats (1998)
    Springer
    Archives of toxicology 72 (1998), S. 541-544 
    Details
    ISSN: 1432-0738
    Keywords: Key words Polychlorinated biphenyl ; Methylsulfonyl metabolite ; Total thyroxine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO2) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO2-2,2′,3′,4′,5,6-hexachlorobiphenyl (3-MeSO2-CB132); 3-MeSO2-2,2′,3′,4′, 5,5′-hexachlorobiphenyl (3-MeSO2-CB141); 3-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (3-MeSO2-CB149) and 4-MeSO2-2,2′,4′,5,5′,6-hexachlorobiphenyl (4-MeSO2-CB149). The congeners were major MeSO2-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO2 metabolites (20 μmol/kg once daily for 4 days) reduced serum total thyroxine levels by 22–44% at a much lower dose than phenobarbital (PB; 431 μmol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO2-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO2-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO2-CB132, 3-MeSO2-CB141 and 3-MeSO2-CB149, but not by 4-MeSO2-CB149. Thus, it is likely that the 3-MeSO2-hexachlorobiphenyls and 4-MeSO2-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO2 metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050540
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  • 114
    Electronic Resource
    Electronic Resource
    Induction by mercury compounds of brain metallothionein in rats: Hg0 exposure induces long-lived brain metallothionein (1998)
    Springer
    Archives of toxicology 72 (1998), S. 187-191 
    Details
    ISSN: 1432-0738
    Keywords: Key words Methylmercury ; Mercury vapor ; Metallothionein ; Brain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to␣most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 μmol/kg per day × 5 days, p.o.) showed brain Hg levels as high as 18 μg/g with slight neurological signs 10␣days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7–8 μg Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for 〉2␣weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002040050486
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  • 115
    Electronic Resource
    Electronic Resource
    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.
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    URL: http://dx.doi.org/10.1007/s004320050148
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    Effects of amperozide, 8-OH-DPAT, and FG 5974 on operant responding for ethanol (1998)
    Springer
    Psychopharmacology 137 (1998), S. 25-32 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alcohol ; Ethanol ; Saccharin ; Self-administration ; Serotonin ; 5-HT1A receptor ; 5-HT2A receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Both 5-HT1A and 5-HT2A receptors have been implicated in modulating ethanol self-administration. A novel serotonergic compound, FG 5974, with combined 5-HT1A agonist/5-HT2A antagonist activities, has shown effects in decreasing ethanol consumption in two-bottle choice paradigms. In the present study, the effect of this compound on operant responding for ethanol (as well as water and a saccharin solution) was compared to compounds possessing the separate neuropharmacological effects of this drug (the 5-HT1A agonist, 8- OH-DPAT, and the 5-HT2A antagonist, amperozide). While all three serotonergic compounds decreased operant responding for ethanol, only FG 5974 had no effect on water and saccharin responding. These results suggest that combined 5HT1A agonist/5-HT2A antagonist activity provides a more selective effect on ethanol reinforcement than either neuropharmacological action alone. Therefore, further analysis of mixed serotonergic compounds in general, and FG 5974 in particular, is warranted as they offer potential treatments for alcoholism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050589
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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 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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    Blockade of the expression of sensitization and tolerance by ondansetron, a 5-HT3 receptor antagonist, administered during withdrawal from intermittent and continuous cocaine (1998)
    Springer
    Psychopharmacology 135 (1998), S. 263-269 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT3 receptor ; Continuous cocaine ; Intermittent cocaine ; Ondansetron ; Sensitization ; Tolerance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The present experiment evaluated the ability of the 5-HT3 antagonist, ondansetron, administered during withdrawal from chronic cocaine administration, to block the expression of sensitization and tolerance induced by the intermittent or continuous administration of cocaine, respectively. Rats were pretreated with 40 mg/kg/per day cocaine for 14 days by either SC injections or osmotic minipumps, or 0.9% saline, administered via osmotic minipump. During the first 5 days of withdrawal from this pretreatment regimen, all rats received a daily SC injection of 0–1.0 mg/kg ondansetron. On day seven of with-drawal from the cocaine pretreatment (2 days after the final ondansetron injection) all subjects received a 15.0 mg/kg IP cocaine challenge. Their behavior was then rated according to the Ellinwood and Balster (1974) scale for 60 min. The results indicated that daily injections of ondansetron, on days 1–5 of withdrawal from the pretreatment regimen, had no significant effect on the subsequent behavioral response to cocaine in the saline control subjects. In contrast, daily injections of ondansetron, on days 1–5 of withdrawal from intermittent cocaine administration, significantly blocked the expression of sensitization. In the continuous cocaine group, ondansetron injections, on days 1–5 of withdrawal from continuous cocaine administration, also blocked the expression of behavioral tolerance. The results therefore indicate that changes in 5-HT3 receptor function are associated with the expression of tolerance and sensitization, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050508
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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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    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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    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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    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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    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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    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.
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    URL: http://dx.doi.org/10.1007/s004240050540
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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.
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    URL: http://dx.doi.org/10.1007/s004240050693
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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).
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    URL: http://dx.doi.org/10.1007/BF01345262
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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.
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    URL: http://dx.doi.org/10.1007/s002130050727
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050728
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  • 131
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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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  • 132
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050540
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  • 133
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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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  • 134
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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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  • 135
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050550
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  • 136
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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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  • 137
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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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  • 138
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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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  • 139
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050650
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  • 140
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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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    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050660
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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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  • 143
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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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050797
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  • 144
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    Effects of glucagon-like peptide-1 (7-36)amide on insulin stimulated rat skeletal muscle glucose transport (1998)
    Springer
    Acta diabetologica 35 (1998), S. 101-103 
    Details
    ISSN: 1432-5233
    Keywords: Key words GLP-1(7-36)amide ; Glucose transport ; Skeletal muscle ; Rat ; Extrapancreatic effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Glucagon-like peptide-1 binding sites have been reported in peripheral tissues including muscle. However, the potential extra-pancreatic effects of glucagon-like peptide-1(7-36)amide are controversial. To evaluate whether glucagon-like peptide-1(7-36)amide has any effects on skeletal muscle glucose transport, isolated rat soleus muscles were incubated in increasing concentrations of insulin (0–150 nmol/l) in the presence or absence of 1 nmol/l glucagon-like peptide-1(7-36)amide for 3 h. Subsequently glucose transport was measured as uptake of [3H]-O-methylglucose. It was found that glucagon-like peptide-(7-36)amide has a small but significant stimulating effect on skeletal muscle glucose transport independent of the insulin concentration (P〈0.01). However, because of the magnitude of the observed effect, the physiological importance of glucagon-like peptide-1 (7-36)amide on skeletal muscle glucose metabolism is questionable.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005920050112
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  • 145
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    Effect of peritransplant FTY720 alone or in combination with post-transplant tacrolimus in a rat model of cardiac allotransplantation (1998)
    Springer
    Transplant international 11 (1998), S. 288-294 
    Details
    ISSN: 1432-2277
    Keywords: Key words FTY720 ; tacrolimus ; heart transplantation ; Tacrolimus ; FTY720 ; heart transplantation ; Heart transplantation ; FTY720 ; tacrolimus ; Rat ; FTY720 ; heart transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract FTY720 is a recently discovered compound that is derived from the fungus Isaria sinclairii. Using a DA donor-to-LEW recipient rat combination, we assessed the efficacy of peritransplant FTY720 alone or in combination with post-transplant tacrolimus on the survival of cardiac allografts. Peritransplant FTY720 given orally at a dose of 5 mg/kg on days –1 and 0 prolonged graft survival from 5 to 13 days (P 〈 0.05). Combining peritransplant FTY720 with post-transplant tacrolimus resulted in a further prolongation of allograft survival. The lymphocyte count in transplanted rats decreased within 24 h to 46.6 %. Analysis of lymphocyte subsets by FACS revealed that FTY720 affected the total population of CD3-bearing T cells while the ratio of CD4 to CD8 cells remained unchanged. Kidney and liver biochemistry remained elevated for 2 weeks. In conclusion, FTY720 is a powerful immunosuppressive agent when used as induction therapy and may have an additive effect – perhaps a synergistic one – with post-transplant tacrolimus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050144
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  • 146
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    Establishment of chimerism in donor liver with recipient-type bone marrow cells prior to liver transplantation produces marked suppression of allograft rejection in rats (1998)
    Springer
    Transplant international 11 (1998), S. S174 
    Details
    ISSN: 1432-2277
    Keywords: Key words Liver transplantation ; Chimerism ; Bone marrow transplantation ; Rat ; FK506
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In this study, we investigated whether establishment of chimerism in donor liver with recipient-type bone marrow cells (BMCs) prior to liver transplantation could prolong the liver allograft survival. Donor female ACI rats were inoculated with recipient-type BMCs of male LEW rats via the portal vein, with or without irradiation as cytoablation, followed by intramuscular administration of FK506 for 5 days. At 1–2 months later, livers were harvested and transplanted into naive female LEW rats. No immunosuppressants were used. Chimerism in donor rats was confirmed by primers specific for the sex determinant Y chromosome of rats. With livers from rats pretreated with recipient-type BMCs, survival of liver allografts was significantly extended, irrespective of irradiation. These results showed that modification of the donor liver by intraportal injection of recipient-type BMCs and concomitant administration of FK506 prior to liver transplantation prolonged liver allograft survival in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001470050455
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  • 147
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    N18-RE-105 cells: differentiation and activation of p53 in response to glutamate and adriamycin is blocked by SV40 large T antigen tsA58 (1998)
    Springer
    Cell & tissue research 291 (1998), S. 191-205 
    Details
    ISSN: 1432-0878
    Keywords: Key words N18-RE-105 cells ; Glutamate ; p53 ; Adriamycin ; Etoposide ; Differentiation ; SV40 large T antigen ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Process extension was induced in cells of the N18-RE-105 neuroblastoma-retinal hybrid line by toxic agents, including glutamate and the p53-inducing anticancer agents adriamycin and etoposide. Both adriamycin and glutamate activated p53 as measured by a plasmid transfection assay. It was therefore hypothesized that SV40 large T antigen, which binds p53, would interfere with cellular differentiation. To test this hypothesis, the temperature-sensitive form of SV40 large T was transduced into N18-RE-105 cells by retroviral infection. SV40 large T-infected cells became de-differentiated, grew in tightly-packed colonies, lost expression of neurofilament, and lost the ability to differentiate in response to glutamate and adriamycin. The de-differentiating effect of SV40 large T antigen may be due to binding and inactivation of cellular proteins, such as p53, p107, p130, p300, and retinoblastoma protein, which are important in cellular growth and differentiation. It is suggested that p53 may play a role in cellular differentiation, perhaps under unusual circumstances involving stress or cytotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410050990
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  • 148
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    Localization of elastin mRNA and TGF-β1 in rat aorta and caudal artery as a function of age (1998)
    Springer
    Cell & tissue research 291 (1998), S. 305-314 
    Details
    ISSN: 1432-0878
    Keywords: Key words Elastin ; TGF-β1 ; Arteries ; In situ hybridization ; Immunohistochemistry ; Northern blot ; Ageing ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Several in vitro studies have previously demonstrated that the addition of TGF-β to aortic smooth muscle cells or skin fibroblasts stimulates elastin synthesis. It is not clear however whether, in vivo, TGF-β participates in the regulation of elastin synthesis, especially in physiological conditions. The aim of our study was to explore the localization of elastin mRNA and TGF-β1 in the rat thoracic aorta (an elastic artery) and caudal artery (a muscular artery). Elastin mRNA was localized by in situ hybridization and quantified using Northern blot analysis. TGF-β1 was detected using immunohistochemistry. The study was carried out as a function of age (rats of 3, 10, 20, and 30 months). We observed that TGF-β1 immunoreactivity is present predominantly, but not exclusively, at the sites of elastin synthesis as determined by elastin mRNA detection: in smooth muscle cells in the aorta and in endothelial cells in the caudal artery. The ability of exogenously added TGF-β1 (0.001–10 ng/ml) to modulate the steady-state levels of elastin mRNA in primary cultures of endothelial cells, smooth muscle cells, and fibroblasts isolated from the thoracic aorta was also studied. At the highest concentration used, elastin mRNA levels increased 5-fold in endothelial cells and 11-fold in smooth muscle cells. The demonstration that TGF-β1 immunoreactivity is present at the sites of elastin synthesis in the thoracic aorta and in the caudal artery and the observation that TGF-β1 induces an increase in elastin mRNA levels in cultured endothelial cells and smooth muscle cells suggest that TGF-β1 may be implicated, at least in part, in the physiological regulation of elastin gene expression.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051000
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  • 149
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    A culture substratum appropriate for brain cells is a chondroitin sulfate glycosaminoglycan in serum (1998)
    Springer
    Cell & tissue research 291 (1998), S. 445-454 
    Details
    ISSN: 1432-0878
    Keywords: Key words Serum-free medium ; Survival ; Chondroitin sulfate ; Culture substratum ; Brain neuron ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  When cells dissociated from the neonatal rat brains are plated on a poly-lysine-coated surface in a serum-free medium, they display a strange morphology: a dark and extended cell body. Preincubation of the surface with fetal bovine serum was found to inhibit the appearance of this strange contraction of the basal cell sheets in a dose-dependent manner. This finding indicated the presence of a factor(s) in the serum, which might be an appropriate substratum for prolonged survival of brain neurons. In the current study, this factor was highly purified through DEAE ion-exchange chromatography followed by gel filtration. The factor was eluted from a Superose column at fractions corresponding to a molecular weight greater than 1000 kDa. By SDS-PAGE analysis, these fractions were found to contain a major band (≥1000 kDa) positive for alcian blue and few minor bands faintly stainable with Coomassie blue. The activity of the purified sample, inducing the morphological change in cells, was diminished by incubation with chondroitinase ABC. Neither heparitinase II, hyaluronidase, nor trypsin modified the activity. An authentic chondroitin sulfate (type B) mimicked the serum action on the morphology of brain cells in early stages of culture. Taking these findings together, it is suggested that the factor in serum beneficial for the attachment of brain cells is composed of a chondroitin sulfate with a Mr greater than 1000 kDa. Cortical cells dissociated from the neonatal rat brain attached well to the purified factor-coated surface and displayed a healthy morphology: an optically-reflective cell body with thick neurites for at least 3 days in the absence of serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051014
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  • 150
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    Double-labeling techniques demonstrate that rod bipolar cells are under GABAergic control in the inner plexiform layer of the rat retina (1998)
    Springer
    Cell & tissue research 292 (1998), S. 17-25 
    Details
    ISSN: 1432-0878
    Keywords: Key words Retina ; Rod bipolar cells ; Amacrine cells ; Protein kinase C ; Glutamic acid decarboxylase ; GABA ; Synaptic circuitry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  The synaptic connectivity between rod bipolar cells and GABAergic neurons in the inner plexiform layer (IPL) of the rat retina was studied using two immunocytochemical markers. Rod bipolar cells were stained with an antibody specific for protein kinase C (PKC, α isoenzyme), and GABAergic neurons were stained with an antiserum specific for glutamic-acid decarboxylase (GAD). Some amacrine cells were also labeled with the anti-PKC antiserum. All PKC-labeled amacrine cells examined showed GABA immunoreactivity, indicating that PKC-labeled amacrine cells constitute a subpopulation of GABAergic amacrine cells in the rat retina. A total of 150 ribbon synapses established by rod bipolar cells were observed in the IPL. One member of the postsynaptic dyads was always an unlabeled AII amacrine cell process, and the other belonged to an amacrine-cell process showing GAD immunoreactivity. The majority (n=92) (61.3%) of these processes made reciprocal synapses back to the axon terminals of rod bipolar cells. In addition, 78 conventional synapses onto rod bipolar axons were observed, and among them 52 (66.7%) were GAD-immunoreactive. Thus GABA provides the major inhibitory input to rod bipolar cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051030
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  • 151
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    Neuronal differentiation is accompanied by NSP-C expression (1998)
    Springer
    Cell & tissue research 292 (1998), S. 229-237 
    Details
    ISSN: 1432-0878
    Keywords: Key words PC12 ; hNT2 ; Neuroblastoma cell lines ; NGF ; Retinoic acid ; Rat ; Human cell lines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Neuroendocrine-specific protein (NSP) reticulons are expressed in neural and neuroendocrine tissues and cell cultures derived therefrom, while most other cell types lack NSP-reticulons. Three major subtypes have been identified so far, designated NSP-A, NSP-B, and NSP-C. We have investigated the correlation between the degree of neuronal differentiation, determined by morphological and biochemical criteria, and NSP-reticulon subtype expression. For this purpose, several human neuroblastoma cell lines, exhibiting different degrees of neuronal differentiation, were examined immuno(cyto) chemically. It became obvious that the expression of NSP-C, as detected by immunofluorescence microscopy and Western blotting, is most prominent in cell lines with a high degree of neuronal differentiation, such as LA-N-5. Such highly differentiated cells also express other neural and neuroendocrine markers, such as neural cell adhesion molecule (NCAM), neurofilament proteins, synaptophysin, and chromogranin. NSP-A was observed in all cell lines to a different extent. However, no clear correlation was observed with the degree of neuronal differentiation as defined by other neuronal and neuroendocrine markers or morphology. NSP-B could not be detected. The induction of neuronal differentiation with nerve growth factor, dbcAMP, and retinoic acid in the rat pheochromocytoma cell line PC12 and the human teratocarcinoma cell line hNT2, respectively, induced the expression of NSP-A and NSP-C in these cell lines parallel to the induction of neurofilament protein expression. It is concluded that NSP-C expression, in particular, is strongly correlated with neuronal differentiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051054
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  • 152
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    Light- and electron-microscopic study of the distribution of axons containing substance P and the localization of neurokinin-1 receptor in bone (1998)
    Springer
    Cell & tissue research 293 (1998), S. 87-93 
    Details
    ISSN: 1432-0878
    Keywords: Key words Osteoclasts ; Osteoblasts ; Osteocytes ; Bone ; Substance P (SP) ; Neurokinin-1 receptor (NK1-R) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Substance P (SP) is a neuropeptide that is released from axons of sensory neurons and causes signal transduction through the activation of the neurokinin-1 receptor (NK1-R). The present study demonstrates the distribution of SP-like-immunoreactive (SP-LI) axons and the localization of NK1-Rs in rat bone tissue using the avidin-biotin-peroxidase complex method. Axons with SP-LI were commonly found near the trabecular bone in the temporal bone marrow, but they were only sparsely distributed in the mandible, femur, and tibia. Immunoreactivity for NK1-Rs was found on the plasma membrane and in the cytoplasm of the osteoclasts. In the osteoblasts and osteocytes, a small number of weak, punctate immunoreactive products of NK1-Rs were distributed close to the plasma membrane. At the electron-microscopic level, immunoreactivity for NK1-R was distributed mainly in the whole cytoplasm, except for the clear zone of the osteoclasts, and in pit-like structures along the plasma membrane. The NK1-R-immunoreactive structures in the cytoplasm were divided into two types of organelles, consisting of vesicular and vacuolar structures (probably transport vesicles and early endosomes). In the osteoblasts and osteocytes, the number of NK1-R-positive vesicular structures was fewer than in the osteoclasts. These results thus suggest that SP secreted by the sensory axons could directly modulate bone metabolism via NK1-Rs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051100
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  • 153
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    The internal and external protein scaffold of the T-tubular system in cardiomyocytes (1998)
    Springer
    Cell & tissue research 294 (1998), S. 449-460 
    Details
    ISSN: 1432-0878
    Keywords: Key words Vinculin ; Talin ; Integrin ; Dystrophin ; Spectrin ; T-tubule ; Costamere ; Basal membrane ; Cardiac muscle cell ; Dilated cardiomyopathy ; Human ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The transverse tubule system of the cardiomyocyte remains undeformed despite the extreme forces it undergoes during the contraction-relaxation cycle, but the morphological basis for its stability remains unclear. Therefore, we have investigated the architecture and subcellular protein scaffold of the cardiac T-tubules and compared it with that of the costameres and of the free sarcolemma. Tissue samples from normal rat and monkey hearts, and left ventricular tissue from normal and cardiomyopathic human hearts obtained at transplantation surgery were investigated using immunocytochemistry and confocal microscopy and by electron microscopy. In addition, we used a re-differentiation model of isolated, cultured adult rat cardiomyocytes. The cell membrane of the cardiac T-tubules was found to contain the cell-matrix focal adhesion molecules (FAMs) vinculin, talin, the α5β1 integrin and the membrane-associated proteins (MAPs) dystrophin and spectrin. FAMs and MAPs were localized in the T-tubular membrane in a similar pattern: in longitudinally oriented myocytes as transverse punctate lines at the Z-level; in transversally cut myocytes a radial tubular network was found to extend throughout the interior of the cell. Immunolabeling for basement membrane components including collagen IV, fibronectin and laminin showed a colocalization with FAMs and MAPs parallel to the transverse T-tubules. The costameres of the sarcolemma showed a protein composition resembling that of the T-tubules but the intervening segments of free sarcolemma showed absence of FAMs and presence of MAPs. For the first time, we demonstrate the existence and protein composition of the T-tubular scaffold in the human heart. Furthermore, we show that cardiomyocytes from human failing hearts have less abundant but more dilated T-tubules than do experimental animals. These results indicate that the cardiac T-tubular system contains a subcellular scaffold closely resembling that of the costameres. It consists of FAMs, MAPs and basal lamina proteins that confer structural integrity to the cardiac T-tubular membrane during contraction/relaxation cycles.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051196
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  • 154
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    Chymotrypsin gene expression in rat peripheral organs (1998)
    Springer
    Cell & tissue research 292 (1998), S. 345-354 
    Details
    ISSN: 1432-0878
    Keywords: Key words Pancreas ; Stomach ; Duodenum ; Ribonuclease protection assay ; Immunocytochemistry ; Protease ; Rat ; (Sprague Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Prior studies have revealed the presence of chymotrypsinlike protease in peripheral organs, although no definitive evidence for the synthesis of this enzyme in tissue other than the pancreas is available. In an attempt to detect chymotrypsinogen mRNA in peripheral organs, a fragment of the pancreatic chymotrypsin mRNA from rat was amplified using PCR. The sequence was identified as a portion of the rat chymotrypsin B gene overlapping exon 5 through exon 7. It was subcloned into the pGEM-4Z vector and used as a template for the vitro transcription of an antisense riboprobe. Using ribonuclease protection and Northern blot analyses, chymotrypsin mRNA was detected in the rat pancreas, stomach, duodenum, ovary, and spleen. Monoclonal and polyclonal antisera against chymotrypsin detected chymotrypsinlike immunoreactivity in rat and human pancreas, rat stomach, duodenum and jejunum. Electrophoresis and immunoblotting revealed chymotrypsin-chymotrypsinogen bands (25–29 kDa) in the stomach and duodenum. Synthesis of a potent protease such as chymotrypsin in tissue other than pancreas is significant, suggesting a potential physiological and/or pathological role in these tissues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051065
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  • 155
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    Specific localization of gap junction protein, connexin45, in the deep muscular plexus of dog and rat small intestine (1998)
    Springer
    Cell & tissue research 292 (1998), S. 487-494 
    Details
    ISSN: 1432-0878
    Keywords: Key words Connexin ; Gap junctions ; Smooth muscle ; Intestinal pacemaker ; Confocal laser scanning microscope ; Dog ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Cellular networks of pacemaker activity in intestinal movements are still a matter of debate. Because gap-junctional intercellular communication in the intestinal wall may provide important clues for understanding regulatory mechanisms of intestinal movements, we have attempted to clarify the distribution patterns of three types of gap junction proteins. Using antibodies for connexin40, connexin43, connexin45, smooth muscle actin, and vimentin, immunocytochemical observations were made with the confocal laser scanning microscope on cryosections of fresh-frozen small intestine and colon of the dog and rat. Connexin 45 was localized along the deep muscular plexus of the small intestine in both dog and rat. Double labeling studies revealed that connexin45 overlapped with vimentin –, but not actin-positive areas, indicating the fibroblast-like nature of the cells, rather than their being smooth muscle-like. Connexin43 immunoreactivity appeared along the smooth muscle cell surface in the outer circular layer of the small intestine of both animals. Connexin 40 immunoreactivity was not observed in the muscle layer other than in the wall of large blood vessels. It is suggested that connexin45-expressing cells along the deep muscular plexus of dog and rat small intestine are likely to act as a constituent of a pacemaker system, which may include a conductive system, by forming a cellular network operating via specific types of gap junctions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051077
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  • 156
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    Calretinin-immunoreactive laminar nerve endings in the laryngeal mucosa of the rat (1998)
    Springer
    Cell & tissue research 292 (1998), S. 613-617 
    Details
    ISSN: 1432-0878
    Keywords: Key words Sensory nerve endings ; Calretinin ; Laryngeal mucosa ; Immunohistochemistry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The distribution of laminar nerve endings that contained immunoreactive calretinin was examined in the laryngeal mucosa of the adult rat. In whole-mount preparations, the immunoreactive laminar endings were distributed in the supraglottic region but not in the subglottic region. The laminar endings that arose from thick nerve fibers with or without swellings were identified as corpuscles with many variform terminal arborizations. They appeared to be located at the interface between the epithelium and the subepithelial connective tissue. The terminals were scattered under the basal lamina of the epithelium, and some of them were located within the epithelial layer. Immunoelectron microscopy revealed that both sub- and intraepithelial immunoreactive terminals that were filled with mitochondria were partly or totally ensheathed by Schwann cell processes. The denervation experiments, in which the superior laryngeal nerve was cut unilaterally or bilaterally, suggested that the laminar endings originate from the superior laryngeal nerve with strict ipsilateral innervation. The laminar endings might be associated with detection of changes in pressure in the laryngeal cavity or chemical stimuli.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051091
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    A novel type of adhering junction in an epithelioid tumorigenic rat cell culture line (1998)
    Springer
    Cell & tissue research 294 (1998), S. 11-25 
    Details
    ISSN: 1432-0878
    Keywords: Key words Adhering junctions ; Desmosomes ; Endothelial junctions ; Plaque proteins ; Desmoplakin ; Cadherins ; Protein ZO-1 ; Rat ; cell culture
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Two major types of plaque-bearing adhering junctions are commonly distinguished: the actin microfilament-anchoring adhaerens junctions (AJs) and the desmosomes anchoring intermediate-sized filaments (IFs). Both types of junction usually possess the common plaque protein, plakoglobin, whereas the other plaque proteins and the transmembrane cadherins are mutually exclusive. For example, AJs contain E-, N-, or P-cadherin in combination with α- and β-catenin, vinculin and α-actinin, whereas in desmosomes, desmogleins and desmocollins are associated with desmoplakin and one or several of the plakophilins (PP1–3). Here we describe a novel type of adhering junction comprising proteins of both AJs and desmosomes and the tight junction (TJ) plaque protein, ZO-1, in a newly established, liver-derived tumorigenic rat cell line (RMEC-1). By immunofluorescence microscopy, cell-cell contacts are characterized by mostly continuous-appearing lines which are usually resolved by electron microscopy as extended arrays of closely spaced small plaque subunits. These plaque-covered regions are positive for plakoglobin, α- and β-catenin, the arm-repeat protein p120, vinculin, desmoplakin and protein ZO-1. They are positive for E-cadherin in cultures early on in passaging, but tend to turn negative for all known cadherins in densely grown cultures. On immunoblotting SDS-PAGE-separated proteins from dense-grown cell monolayers, “pan-cadherin” antibodies have reacted with a band at ∼140 kDa, identified as N-cadherin by peptide fingerprinting of the immunoprecipitated protein, which for reasons not yet clear is modified or masked in immunolocalization experiments. The exact histological derivation of RMEC-1 cells is not known. However, the observations of several endothelial markers and the fact that all cells are rich in IFs containing vimentin and/or desmin, while only subpopulations also reveal IFs containing CKs 8 and 18, is suggestive of a mesenchymal, probably endothelial origin. We discuss the molecular relationship of this novel type of extended junction with other types of adhering junctions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051152
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  • 158
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    Effects of growth rate and cell density on nerve growth factor secretion in cultures of vascular and bladder smooth muscle cells from hypertensive and hyperactive rats (1998)
    Springer
    Cell & tissue research 294 (1998), S. 431-438 
    Details
    ISSN: 1432-0878
    Keywords: Key words Nerve growth factor ; Hypertension ; Contact inhibition ; Proliferation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Elevated target-derived smooth muscle nerve growth factor (NGF) and resultant neurogenic plasticity are associated with both hypertension and hyperactive voiding in spontaneously hypertensive rats (SHRs: hypertensive, behaviorally hyperactive). In culture, vascular (VSMCs) and bladder (BSMCs) smooth muscle cells derived from SHRs secrete higher levels of NGF, proliferate more rapidly, and achieve higher density at confluence than do control Wistar-Kyoto (WKY) cells. To elucidate growth-related contributions to the elevated tissue NGF observed in SHRs, we examined vascular VSMC and BSMC NGF secretion in two inbred cell lines (WKHTs, hypertensive; WKHAs, hyperactive) derived from SHRs and WKYs to assess the phenotypic association of altered NGF metabolism with either hypertension or behavioral hyperactivity. Cell density, rather than growth rates, was the most important factor with respect to NGF secretion. VSMC density varied such that WKHT=SHR〉WKY= WKHA, higher VSMC density being associated with higher NGF output. However, in BSMC cultures, NGF output was the lowest in high density cell lines, with WKHT〉SHR〉WKY〉WKHA. SHR BSMCs had the second highest cell density and NGF secretion level. Elevated packing density, presumably because of a lack of contact inhibition, co-segregated with the hypertensive phenotype in both VSMCs and BSMCs. Thus, dysfunctional smooth muscle growth characteristics may contribute to the augmented vascular and bladder NGF content associated with high blood pressure and hyperactive voiding in SHRs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051194
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  • 159
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    Loss of myocardial capillary endothelial-cell alkaline phosphatase (ALP) activity in primary endothelial cell culture (1998)
    Springer
    Cell & tissue research 291 (1998), S. 497-505 
    Details
    ISSN: 1432-0878
    Keywords: Key words Endothelial cells ; Alkaline phophatase ; Primary cultures ; Proliferation ; Gene expression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Primary cultures of rat myocardial capillary endothelial cells were established and characterized. A range of typical endothelial cell-specific markers were retained in vitro. Cell kinetic studies in confluent endothelial-cell cultures in vitro revealed a roughly 50-fold increase in the proportion of cells in s-phase, indicating a very considerable shortening of cell turnover time, compared to in vivo conditions. Alkaline phosphatase enzyme activity and encoding mRNA are strongly expressed in myocardial capillary endothelial cells in vivo, but were not detectable in vitro. This was true in cell cultures from two strains of rat, which revealed significantly different enzyme expression levels in vivo. In co-cultures of pericytes and endothelial cells, positive ALP enzyme reaction was detected in pericytes, which in vivo show only very weak enzyme reactivity. Treatment of cell cultures with ≤10 M retinoic acid had no effect in pure endothelial cell cultures, but did increase ALP expression of pericytes in co-cultures. The observation of a loss of endothelial ALP expression in vitro supports other in vitro as well as our own in vivo observations, indicating a negative correlation of ALP expression and proliferative activity of endothelial cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051019
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  • 160
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    Polysome-like structures in the chromatoid body of rat spermatids (1998)
    Springer
    Cell & tissue research 291 (1998), S. 575-579 
    Details
    ISSN: 1432-0878
    Keywords: Key words Chromatoid body ; Polysomes ; RNA ; Spermatid ; Spermatogenesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  A procedure for isolating the chromatoid body from the testis of 40-day-old rats was developed. Electron-microscopical analysis indicated that about 70% of the isolated organelles were chromatoid bodies, while the remaining structures corresponded to dense bodies and probably to satellites. Negative staining of the isolated organelles revealed the presence of polysome-like structures in about 20% of the chromatoid bodies suggesting that the polysomes were not due to contamination with cytoplasmic polysomes. Moreover, the presence of RNA in the stroma of the chromatoid body was confirmed by RNAse-gold staining. Preliminary electrophoretic analysis of the RNA extracted from the organelles revealed the presence of a complex population of RNAs including 5.8 and 5 S ribosomal RNAs but no tRNA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051027
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  • 161
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    Edema formation in the rat larynx (1998)
    Springer
    Cell & tissue research 292 (1998), S. 367-375 
    Details
    ISSN: 1432-0878
    Keywords: Key words Larynx ; Edema ; Mast cells ; Compound 48/80 ; Substance P ; Capsaicin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  In the rat larynx, plasma exudation and edema formation were studied by light and electron microscopy after i.v. injections of the mast cell activator compound 48/80, substance P, and capsaicin. The morphological effects of substance P and capsaicin on connective tissue mast cells in vivo were also examined. Of the drugs tested, only compound 48/80 degranulated the connective tissue mast cells. All drugs induced a subepithelial plasma exudation in the subglottic region, with edema in the lamina propria and widened intraepithelial intercellular spaces, though the tight junction regions seemed intact. In the epiglottis, 10 min after compound 48/80 injection, there was edema in the lamina propria on the lingual side, with an intact and tight epithelial lining. No morphological sign of edema was found in the epiglottis after injection of substance P or capsaicin. The pronounced effect found in the epiglottic region after compound 48/80 injection was due to the release of mediators such as histamine and 5-hydroxytryptamine from the connective tissue mast cells. This study supports the belief that substance P in vivo mediates an increased vascular permeability by a direct effect on the blood vessels – a mechanism distinct from mast cell degranulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051067
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  • 162
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    Internal division of capillaries in rat skeletal muscle in response to chronic vasodilator treatment with α1-antagonist prazosin (1998)
    Springer
    Cell & tissue research 293 (1998), S. 293-303 
    Details
    ISSN: 1432-0878
    Keywords: Key words Angiogenesis ; Capillary growth ; Prazosin ; Shear stress ; Skeletal muscle ; Ultrastructure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Chronic vasodilatation represents a stimulus for capillary growth associated with increased luminal shear stress. We have examined the ultrastructure of more than 2000 capillaries to establish whether the sequence of angiogenesis in response to this stimulus is similar to that described during development and under pathological circumstances. Administration of the α1-blocker prazosin to rats for 2 weeks led to a greater capillary length density in extensor hallucis proprius muscles without any change in capillary tortuosity: J v(c,f)=262±54 compared with 350±17 mm–2, control compared with prazosin (P〈0.002). There were obvious signs of endothelial cell (EC) activation after prazosin treatment, including an increased proportion of capillaries with rough endoplasmic reticulum, large cytoplasmic vacuoles, thickened endothelium and an irregular luminal surface. Capillaries from control muscles had a maximum of three ECs in cross section, whereas four ECs were noted in 0.8+0.5% of capillaries after 1 week (n.s.) and 2.5±0.9% after 2 weeks (P〈0.01) of treatment. This could be due to elongation and/or migration of ECs, as cell proliferation has not been described at these time points. There was also an increase in the proportion of capillaries having a narrow, slit-like lumen (1.7±0.8% of controls; 7.1±1.9% at 1 week; 8.8±2.5% at 2 weeks; P〈0.02), some of which were smaller in size (less than 2 μm diameter) than in controls (3–5 μm) and/or “seamless”, i.e. lacking EC junctions. These may represent newly formed vessels. Focal discontinuity of the basement membrane and abluminal EC processes were rarely seen, and capillary growth by abluminal sprouting appeared to be very infrequent (less than 0.001% of profiles). Of more importance was growth starting from the luminal side. Significantly more thin cytoplasmic processes were observed protruding into the lumen of capillaries after 1 week (47.5±6.2%, P〈0.001) and 2 weeks of prazosin (34.2±5.5%, P〈0.05) than in control vessels (16.7±3.9%). Some of these traversed the entire lumen and connected with endothelium of the opposite side, probably involving membrane fusion, resulting in the appearance of a double lumen. Individual capillaries with a complete double lumen were observed after 2 weeks’ prazosin but comparatively rarely, in only four out of six muscles. These findings indicate a pattern of luminal growth which is completely different from intussusceptive growth previously described during development, and from the abluminal capillary sprouting seen under pathological circumstances.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004410051121
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  • 163
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    Flow-driven Diameter Response in Rat Femoral Arteries Perfused In Vitro (1998)
    Springer
    Annals of biomedical engineering 26 (1998), S. 526-533 
    Details
    ISSN: 1573-9686
    Keywords: Rat ; Artery: femoral ; Arterial diameter ; Vasomotion ; Shear stress ; Flow-dependent constriction ; Step flow ; Oscillating flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract The effects of flow and flow changes on arterial diameter were investigated in vitro on isolated rat femoral arteries. Segments of femoral arteries were excised, mounted on microcannulas, and perfused with Tyrode's solution (37°C). Perfusion pressure was kept constant at 90 mm Hg. The mean external diameter after equilibration at a transmural pressure of 90 mm Hg was 720 ± 50 μ m (n=12). Vessels were then constricted with norepinephrine (1 μM in the superfusion solution) to 77% ± 13% of the resting diameter; acetylcholine was used to check endothelial function. The external diameter was measured continuously using video microscopy. The arteries were subjected to two different types of flow variations: (a) step changes in flow (increase and decrease, n=6) and (b) low-frequency sinusoidal flow variations (frequencies ranging from 0.002 to 0.1 Hz, n=11). Flow ranged from 0 to 800 μ l/min (shear stress ranging from 0 to 15 dyn/cm2). All measured vessels constricted as flow increased. Flow steps induced exponential-like contractions (flow increase) or relaxations (flow decrease) with mean characteristic time constants 31 ± 4 and 22 ± 2 s, respectively. Sinusoidal flow oscillations induced sinusoidal diameter oscillations with a time delay. An increase in the frequency of the flow led to a decrease of both the amplitude of the flow-induced diameter oscillations and the phase shift between flow and diameter. The dynamic diameter response to flow changes could be characterized by a first-order low-pass filter with a time constant of 22 s. © 1998 Biomedical Engineering Society. PAC98: 8745Hw
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.99
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  • 164
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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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  • 165
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    The rate model of endocarditis (1998)
    Springer
    Methods in cell science 20 (1998), S. 203-207 
    Details
    ISSN: 1573-0603
    Keywords: Endocarditis ; Rat ; Streptococci
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The rat model of endocarditis is a well established experimental protocol which closely approximates human native valve endocarditis. The rat model of endocarditis has been used to examine the role of particular streptococcal virulence factors, to assess immunoprotective strategies, and to evaluate the efficacy of selected antibiotic treatment regimens for streptococcal endocarditis. Like humans, rats are generally susceptible to endocarditis only if the cardiac valves have been damaged. In the rat model of endocarditis, damage to the aortic valve and sterile vegetation formation is accomplished by insertion of a polyethylene catheter through the carotid artery into the left ventricle. Following catheter insertion, an inoculum of streptococci are injected intravenously. Vegetations removed from the heart valves during thoracotomy of euthanized animals are qualitatively cultured for streptococcal infection. The method, including investigator safety considerations, is described in detail.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009719802803
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  • 166
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    Partial replacement of dietary casein with soy protein isolate can reduce the severity of retinoid-induced hypertriglyceridemia (1998)
    Springer
    Plant foods for human nutrition 52 (1998), S. 97-108 
    Details
    ISSN: 1573-9104
    Keywords: Hypertriglyceridemia ; Protein ; Rat ; Retinoid ; Soy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Previous research carried out in an animal model of retinoid-induced hypertriglyceridemia – rats fet a 13-cis retinoic acid (13cRA)-containing diet having casein as the protein source – has demonstrated that the complete replacement of dietary casein with soy protein isolate (SPI) can decrease the severity of this condition. In this study, the effect of partially replacing dietary casein with SPI was investigated. Five groups of male Fischer 344 rats were used in a 14-day study, with two groups being fed diets having casein as the protein source, without or with 13cRA (groups A and B, respectively), and three groups being fed 13cRA-containing diets in which SPI was used to bring about the isonitrogenous replacement of 25, 50, or 100% of the casein in the formula for the diet used for group B (groups C-E, respectively). Serum triglyceride concentration for group B was significantly different ( p 〈 0.05) from that of groups A, D, and E (5.41 vs 2.62, 4.04, and 2.66 mmol/l, respectively). Serum cholesterol concentrations for groups D and E were significantly lower ( p 〈 0.05) than for groups A and B (1.63 and 1.60 vs 2.00 and 2.14 mmol/l, respectively). Thus, the isonitrogenous replacement of 50% of dietary casein with SPI can reduce the severity of retinoid-induced hypertriglyceridemia while decreasing the serum concentration of cholesterol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008092906465
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    A Computational Analysis of FXa Generation by TF:FVIIa on the Surface of Rat Vascular Smooth Muscle Cells (1998)
    Springer
    Annals of biomedical engineering 26 (1998), S. 28-36 
    Details
    ISSN: 1573-9686
    Keywords: Mathematical model ; Tissue factor ; Wall shear rate ; FXa generation ; TF:FVIIa ; Rat ; Vascular ; Smooth muscle ; Factor X ; Coagulation ; Clot
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract A computational model was developed to investigate the contribution of classical mass transport and flow parameters to factor X (FX) activation by the tissue factor–factor VIIa complex (TF:VIIa) on one wall of a parallel-plate flow chamber. The computational results were compared to previously obtained experimental data for the generation of factor Xa (FXa) by TF:VIIa on the surface of cultured rat vascular smooth muscle cells. In this study, the complete steady-state convection–diffusion equation was solved using the commercial software package, FLUENT (Fluent Inc., Lebanon, New Hampshire). A user-defined subroutine interfaced with FLUENT implemented the surface reaction which was modeled using classical Michaelis–Menten reaction kinetics. The numerical solutions were obtained for 12 cases which used combinations of three wall shear rates and four reaction rates. The numerically obtained fluxes for a given reaction rate displayed a wall shear rate dependence which ranged from classical kinetic reaction control (no dependence) to pure diffusional control (maximum dependence). The experimental data, however, were not represented by numerical data generated using a single reaction rate. The three numerically obtained fluxes which corresponded most closely to the experimental fluxes were determined using three different V max values. This finding supports the hypothesis that there may be a direct effect of flow on the TF:VIIa complex or the cell membrane. © 1998 Biomedical Engineering Society. PAC98: 8722-q, 8710+e
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1114/1.120
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  • 168
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    Delayed neuronal cell death and microglial cell reactivity in the CA1 region of the rat hippocampus in the cardiac arrest model (1998)
    Springer
    Medical molecular morphology 31 (1998), S. 85-93 
    Details
    ISSN: 1860-1499
    Keywords: Ischemia ; Delaved neuronal cell death ; Apoptosis ; Microglia ; Electron microscopy ; Rat ; Hippocampus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Morphological changes in the CA1 region of the hippocampus in the rat cardiac arrest model were studied with the in situ nick-end labeling (TUNEL) method and light and electron microscopy. The TUNEL-positive pyramidal cells first appeared on day 1, increased in number with time, and reached a peak at 7 days after recirculation. At the ultrastructural level, cell shrinkage, nuclear fragmentation, and an increased number of atuophagic vacuoles of the pyramidal cells were observed in the CA1 region. The brief ischemia activates the microglial cells in the CA1 region, and these cells were found to increase in number with time. The microglial cells were seen to adhere to degenerating pyramidal cells and to phagocytose the apoptotic neurons selectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01557785
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    Effects of renovascular hypertension on myocardial protein patterns: Analysis by computer-assisted two-dimensional gel electrophoresis (1998)
    Weinheim : Wiley-Blackwell
    Electrophoresis 19 (1998), S. 2043-2050 
    Details
    ISSN: 0173-0835
    Keywords: Rat ; Heart proteins ; Renovascular hypertension ; Two-dimensional polyacrylamide gel electrophoresis ; Computer-assisted gel analysis ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Hypertensive heart disease caused by renovascular hypertension reflects the response of the heart to an increased afterload and neurohormonal stimulation. We hypothesized that in this condition the composition of the myocardial proteins of rats was altered. To identify yet unknown quantitative and qualitative differences in myocardial proteins in renovascular hypertensive heart disease, we analyzed protein patterns by computer-assisted two-dimensional polyacrylamide large gel electrophoresis. Renovascular hypertension was induced by placing a silver clip on the left renal artery in 9-week-old rat siblings. Sham-operated animals served as controls. Systolic blood pressure (197 ± 19 mm Hg) and heart/body weight ratios (0.36 ± 0.04%) were significantly increased in the hypertensive animals. Twenty protein patterns from the left ventricle of five hypertensive and five control rats were compared. The molecular mass and isoelectric point (pI) of proteins spots ranging from 13 to 100 kDa and from 4.5 to 8.5, respectively, were determined using marker proteins. In total, 761 ± 88 protein spots were resolved in all twenty gels. For the quantitative data analysis a univariate (Mann-Whitney test) as well as a multi-variate statistical approach (correspondence analysis) were applied. Only one myocardial protein spot (molecular mass = 41.3 kDa; pI = 6.3) was decreased by more than twofold (p 〈 0.05) in renovascular hypertension. The vast majority of spots did not indicate a significant alteration of intensity. Left ventricular hypertrophy in early renovascular hypertension induces a form of myocardial hypertrophy that conserves the naturally occurring protein expression pattern.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elps.1150191124
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    Differential expression of cytosolic proteins in the rat kidney cortex and medulla: Preliminary proteomics (1998)
    Weinheim : Wiley-Blackwell
    Electrophoresis 19 (1998), S. 2491-2497 
    Details
    ISSN: 0173-0835
    Keywords: Cortex ; Cytoplasm ; Two-dimensional polyacrylamide gel electrophoresis ; Kidney ; Medulla ; Proteomics ; Rat ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: The rodent kidney is a target of many xenobiotics and is typified by regionally specific structure and function. This renders distinct regions of the kidney differentially susceptible to toxic exposure and effect. To characterize these differences at the proteome level, protein patterns from male rat kidney cortex and medulla cytosols were examined by two-dimensional electrophoresis (2-DE) and image analysis and prominent proteins identified immunologically or by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) and electrospray/ionization - tandem mass spectrometry (ESI-MS/MS) sequence tag identification. An average of 727 protein spots were resolved and matched to the cortex cytosol reference pattern, and 716 in the medulla. Of this total, 127 proteins were found to differ in abundance (86 higher in cortex; 41 higher in medulla) (P 〈 0.001). Of those proteins that were detectable in both cortex and medulla, the abundance of 97 differed significantly while 30 proteins were found to be unique to one region or the other (26 in cortex, 4 in medulla). Twenty protein spots were identified and their regional differences are discussed. These results both confirm and expand our understanding of the molecular heterogeneity characterizing structurally and functionally distinct regions of the kidney and serve as a useful foundation for future nephrotoxicologic studies.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/elps.1150191423
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  • 171
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    Importance of catecholestrogens in the regulation of the ovarian cycle (1982)
    Springer
    Archives of gynecology and obstetrics 231 (1982), S. 315-320 
    Details
    ISSN: 1432-0711
    Keywords: Ovarian cycle ; Physiology ; Catecholestrogens ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using highly stabilized catecholestrogen preparations-ascorbic acid added to the free alcohols or benzoic acid derivatives — 2- and 4-hydroxyestrogens were tested in simple, clearly defined animal models: As index for the peripheral action the influence on vaginal opening and uterus weight gain was monitored after continuous s.c. administration for 6 days (minipumps) in immature intact rats resulting in a relative estrogenic potency (estradiol = 100%) of 70–100% for 4-hydroxyestradiol and less than 30% for 2-hydroxyestradiol. As index for the central action LH levels were measured in adult ovx rats leading to the same relations in the relative potencies. As index for both central and peripheral actions LH levels and the formation of corpora lutea were investigated in animals with an intact but prepubertal feed-back loop, i.e. in 25-day-old immature rats. 4-Hydroxyestradiol in this model clearly triggered LH surges and induced ovulations, its potency being in the same range as that of estradiol. 2-Hydroxyestradiol, in comparable doses, again showed no significant effect. Finally, female immature animals known to ovulate 3 days after PMS injection were treated concomitantly with either primary or catecholestrogen-antibody preparations. Whereas the primary estrogen antibody significantly blocked ovulation, the 2- and 4-hydroxyestrogen antibodies were ineffective. If, however, PMS and estrogen-antibody treated animals were supplemented with 4-hydroxyestrogens, ovulations could be restored. Thereby, it was inferred that peripheral 4-hydroxyestrogens, though not essential for the physiology of reproduction, can completely replace the physiologically essential peripheral estradiol at central target sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02111730
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    Interrelations of the rat's thalamic reticular and dorsal lateral geniculate nuclei (1982)
    Springer
    Experimental brain research 45 (1982), S. 217-229 
    Details
    ISSN: 1432-1106
    Keywords: Rat ; Thalamic reticular nucleus ; Lateral geniculate nucleus ; Electrophysiology ; HRP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Electrophysiological and neuroanatomical techniques have been used to study the properties of cells in the reticular nucleus of the thalamus (RNT) responsive to photic stimuli. In the rat these cells are located in a discrete region of the nucleus lying immediately rostral to the dorsal lateral geniculate nucleus (LGNd), where the visual field is represented in a retinotopic fashion. After injections of horseradish peroxidase (HRP) into this area, neurones labelled with reaction product were found in the LGNd and not in other thalamic relay nuclei. After HRP injections into the LGNd, labelled RNT cells were found only within the region which contains neurones responsive to photic stimuli. These observations suggest that there is a precise reciprocal relation between the two areas. Studies and comparisons of the responses of relay cells (P cells) in LGNd and cells in RNT to electrical shocks lead us to conclude that RNT cells receive their excitation mainly via those relay cells in LGNd which are themselves excited by fast-conducting retinal ganglion cell axons. Such cells in LGNd have phasic responses and concentric receptive fields while RNT cells have phasic responses and on/off fields and a comparison of the receptive field sizes of P cells and RNT cells suggests that only a small number of LGNd relay cells converge on to each RNT cell. Further, although a particular functional class of relay cells in LGNd (Y-type) is shown to provide the major input to visually responsive RNT cells, both Y type and W type relay cells are subject to their inhibitory control. These results furnish evidence that cells in the RNT have an important role in modulating the flow of visual information from the LGNd to cortex.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235781
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    Apomorphine-induced ipsilateral turning in rats with unilateral lesions of the parafascicular nucleus (1982)
    Springer
    Experimental brain research 47 (1982), S. 270-276 
    Details
    ISSN: 1432-1106
    Keywords: Rat ; Turning ; Parafascicular nucleus ; Fasciculus retroflexus ; Apomorphine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Apomorphine, 2 mg/kg i.p., produced ipsilateral turning in rats with unilateral lesions in the parafascicular nucleus of the thalamus. The effect was completely blocked by the administration of haloperidol, 0.3 mg/kg i.p. There were no asymmetries by the lesions alone or after administration of haloperidol, 2 mg/kg i.p. to lesioned animals. In control experiments apomorphine produced a marked contralateral turning in animals with unilateral degeneration of the fasciculus retroflexus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00239386
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    The effect of prenatal exposure to diazepam on aspects of postnatal development and behavior in rats (1982)
    Springer
    Psychopharmacology 78 (1982), S. 225-229 
    Details
    ISSN: 1432-2072
    Keywords: Diazepam ; Prenatal treatment ; Development ; Discrimination ; Motor behavior ; Learning retention ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study the effects of chronic treatment of pregnant rats with diazepam on the physical and behavioral development of their offspring were investigated. Rats that were diazepam-exposed prenatally were compared to age-matched controls in terms of the following: number of littermates; birth weight and weight gain until weaning; motor development and coordination; simple motor learning; open field activity; performance on learning tasks of varving complexity; retention of these tasks. Nulliparous Wistar rats were injected s.c. for 16 days of their pregnancy with either 2.5, 5, or 10 mg/kg diazepam or an equal volume of vehicle. Prenatal diazepam treatment did not alter litter size, birth weight, or the righting reflex, but seemed to retard early motor development transiently. Diazepam pups showed longer latencies and less rearing in the open field. There were no differences between animals exposed to drug and vehicle in simple motor learning or in acquiring a simple successive discrimination task. However, there were significant dosedependent differences on a complex six-choice simultaneous discrimination learning task, the diazepam-exposed rats making more errors and taking more time to reach the goal. A significant difference was seen again between diazepam-and vehicle-exposed rats on the retention test 10 days later. The results indicate that diazepam administered to pregnant rats has long-range effects on the behavior of the offspring, some becoming manifest even in maturity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428155
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    A study of the role of the cholinergic system in amygdaloid kindling in rats (1982)
    Springer
    Psychopharmacology 76 (1982), S. 66-69 
    Details
    ISSN: 1432-2072
    Keywords: Experimental epilepsy ; Kindling ; Amygdala ; Acetylcholine ; Choline uptake ; Atropine ; Muscarinic receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of atropine on kindling the amygdala of rats was tested by administering the drug in a dose of 25 mg/kg 1 h before each stimulus was applied. Rats tested with atropine kindled at the same rate as saline-treated controls. Cholinergic activity in the amygdala of rats was assessed, 4 weeks after the completion of kindling, by measuring both muscarinic receptor numbers and sodium-dependent high affinity choline uptake in tissue homogenates. There was no change in either of these parameters attributable to kindling. These results suggest that changes in the cholinergic system are not fundamental either to the development or the maintenance of kindling in the rat amygdala.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430758
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  • 176
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    Reduced brain serotonergic activity after repeated treatment with β-adrenoceptor antagonists (1982)
    Springer
    Psychopharmacology 76 (1982), S. 114-117 
    Details
    ISSN: 1432-2072
    Keywords: Brain ; β-Adrenoceptors ; Serotonin synthesis ; Metoprolol ; ICI 118,551 ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were treated subchronically (14 days) or acutely (single dose) with the β1-selective adrenoceptor antagonist metoprolol or the β2-selective adrenoceptor antagonist ICI 118,551. Metoprolol (350 mg/kg/day for 14 days, orally) significantly reduced the 5-hydroxytryptophan (5-HTP) accumulation when measured 30 min after inhibition of L-amino acid decarboxylase by NSD 1015 (100 mg/kg IP) in the limbic forebrain, the corpus striatum, the cerebral cortex, the brain stem, and in the cerebellum. ICI 118,551 (0.5 mg/kg, twice daily for 14 days, SC) also significantly reduced the 5-HTP accumulation in the same brain regions except in the corpus striatum and the brain stem. Simultaneously assayed tryptophan levels were largely unaffected. Thus sustained β-adrenoceptor blockade causes a decrease in the in vivo rate of tryptophan hydroxylation in various rat brain regions. The subchronic treatments with metoprolol or ICI 118,551 also significantly reduced the endogenous levels of 5-hydroxytryptamine (5-HT) in the various rat brain regions studied. Acute treatment with either metoprolol (2 mg/kg SC) or ICI 118,551 (0.5 mg/kg SC) did not affect the 5-HTP accumulation or the endogenous 5-HT levels in the brain regions studied. This inhibitory effect on brain 5-HT systems produced by sustained β-adrenoceptor blockade may be of significance both for the long-term cardiovascular action and for occasional neuropsychiatric side effects during β-blocking therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00435263
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    Effects of chronic nicotine administration on the response and adaptation to stress (1982)
    Springer
    Psychopharmacology 76 (1982), S. 160-162 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Withdrawal ; Plasma corticosterone ; Stress ; Adaptation ; 5-Hydroxytryptamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of chronic nicotine administration (0.4 mg/kg for 40 days) and its withdrawal on the adrenocortical response to acute and repeated exposure to stress have been examined and related to changes in brain 5-hydroxyindole levels. No significant effects on the response to acute stress were observed. Repeated exposure to the stressful procedure resulted in complete adaptation of the adrenocortical response and the development of a significant (P〈0.01) positive correlation between the plasma corticosterone and hippocampal 5-HT concentrations. In nicotine-treated rats, complete adaptation did not occur and the plasma corticosterone showed a significant (P〈0.05) negative correlation with hippocampal 5-HT. Nicotine withdrawal was not associated with any reduction in plasma corticosterone, but did abolish its relationship with hippocampal 5-HT.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00435271
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  • 178
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    Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphé nuclei (1982)
    Springer
    Psychopharmacology 78 (1982), S. 261-265 
    Details
    ISSN: 1432-2072
    Keywords: Turning behaviour ; Brain lesions ; 5-MeODMT ; Dopaminergic system ; Dopamine release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The turning behaviour induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) has been investigated in rats with lesions of the dorsal raphé nucleus (DRN). 5-MeODMT caused a dose-related contralateral turning in rats with 5,7-dihydroxytrypamine (5,7-DHT) lesions of the substantia nigra and a similar effect was observed in DRN-lesioned rats. In contrast, a dose-related ipsilateral turning was observed when 5-MeODMT was injected into rats with 5,7-DHT lesions of the striatum. These results suggest that the effects of 5-MeODMT in DRN-lesioned rats are mediated via the substantia nigra. The contralateral turning induced by 5-MeODMT in rats with a 5,7-DHT lesion of the DRN was significantly reduced when a second 6-hydroxydopamine lesion was placed in the striatum, but not when it was placed in the nucleus accumbens. Thus the nigrostriatal dopaminergic system seems to be involved in 5-MeODMT-induced turning. The release of tritium from slices of substantia nigra previously labelled with [3H]-dopamine was inhibited by 5-MeODMT (10-7 to 10-5 M) and this effect was blocked by methysergide in a concentration-related manner. Tetrodotoxin (10-7M) failed to antagonise 5-MeODMT. These results suggest that 5-MeODMT can inhibit dopamine release from nigral dendrites, which could in turn enhance nigrostriatal activity by reducing the auto-inhibitory actions of dopamine, thereby causing contralateral turning in DRN-lesioned rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428162
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  • 179
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    Does conditioned nausea mediate drug-induced conditioned taste aversion? (1982)
    Springer
    Psychopharmacology 78 (1982), S. 277-281 
    Details
    ISSN: 1432-2072
    Keywords: Conditioned taste aversion ; Scopolamine ; Prochlorperazine ; Lithium ; Amphetamine ; Morphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two antiemetic drugs were tested on the expression of taste aversions previously conditioned in rats with lithium, amphetamine or morphine. Neither prochlorperazine nor scopolamine administered prior to testing attenuated established aversions, although both drugs are known to have antiemetic effects in other species. Negative findings were obtained with a range of doses of prochlorperazine and scopolamine, with strong and weak aversions, with one- and two-stimulus tests, in a repeated one-stimulus extinction procedure, with between- and within-group designs and with hooded, albino, male and female rats. The results do not support the widely accepted hypothesis that conditioned nausea mediates conditioned taste aversion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428165
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  • 180
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    Lack of evidence for a role of endorphinergic mechanisms in mediating a discriminative stimulus produced by diazepam in rats (1982)
    Springer
    Psychopharmacology 78 (1982), S. 282-284 
    Details
    ISSN: 1432-2072
    Keywords: Discriminative stimulus ; Diazepam ; Morphine ; Naloxone ; Endorphins ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Sprague-Dawley rats were trained in a two-lever food-reinforced procedure to discriminate between the effect of saline and diazepam (2.5 mg/kg). After acquisition of this discrimination, the ability of morphine to generalize, and naloxone to antagonize the diazepam discriminative stimulus was tested. The rats did not generalized the effect of morphine, and naloxone did not antagonize the diazepam discriminative stimulus whether it was given prior or subsequent to diazepam. These data suggest a lack of involvement of endorphins in mediating the discriminative stimulus property of diazepam.
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    URL: http://dx.doi.org/10.1007/BF00428166
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  • 181
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    Using Ro 15-1788 to investigate the benzodiazepine receptor in vivo: Studies on the anticonvulsant and sedative effect of melatonin and the convulsant effect of the benzodiazepine Ro 05-3663 (1982)
    Springer
    Psychopharmacology 78 (1982), S. 293-295 
    Details
    ISSN: 1432-2072
    Keywords: Seizure threshold ; Ro 15-1788 ; Ro 05-3663 ; Benzodiazepine receptor ; Melatonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both the anticonvulsant and sedative effects of diazepam (5 mg/kg) were reversed by subsequent administration of the suggested specific benzodiazepine antagonist Ro 15-1788. In contrast neither the seizure threshold raising or sedative effect of melatonin (200 mg/kg) was reversed by Ro 15-1788. Ro 15-1788 had no effect on the convulsant action of the benzodiazepine Ro 05-3663. These data therefore argue against the suggestion that melatonin produces its sedative and anticonvulsant effects in vivo by interacting with the benzodiazepine receptor, and also strengthens the suggestion that Ro 05-3663 does not act at this site. The use of Ro 15-1788 in demonstrating whether a drug acts in vivo at the benzodiazepine site to produce a pharmacological response is discussed.
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    URL: http://dx.doi.org/10.1007/BF00428169
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  • 182
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    Influence of lisuride on morphine withdrawal signs in the rat: A dopamine-mimetic effect (1982)
    Springer
    Psychopharmacology 78 (1982), S. 326-330 
    Details
    ISSN: 1432-2072
    Keywords: Morphine withdrawal ; Dopamine ; Lisuride ; N-n-propylnorapomorphine ; Haloperidol ; Sulpiride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of lisuride on naloxone-induced withdrawal signs (wet shakes, escape attempts) was studied in morphine-dependent rats. Lisuride, injected IP at doses of 12.5 and 25 μg/kg, inhibited wet shakes while not significantly altering escape attempts induced by naloxone (4 mg/kg IP). At higher doses (50 and 100 μg/kg IP), lisuride's inhibitory effect on wet shakes persisted while escape attempts were actually potentiated with respect to control withdrawal rats. Increases in aggressive behavior were seen at all doses, and were dose-related. Haloperidol (0.3 mg/kg IP), administered 40 min before lisuride, did not modify the antagonistic effect on wet shakes, unlike sulpiride (40 mg/kg IP 30 min before lisuride), but at the same time blocked the increase in escape attempts and aggressiveness induced by lisuride. We suggest that lisuride modulates withdrawal signs by stimulation of dopamine receptors in the CNS. The effect of the dopamine mimetic N-n-propylnorapomorphine (NPA) on the same variables is reported as well as the influence of haloperidol on NPA, and a comparison between the effects of the two drugs is made.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433735
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  • 183
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    Feeding stimulated by very low doses of d-amphetamine administered systemically or by microinjection into the striatum (1982)
    Springer
    Psychopharmacology 78 (1982), S. 336-341 
    Details
    ISSN: 1432-2072
    Keywords: d-Amphetamine ; Feeding ; Locomotion ; Stereotypy ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of d-amphetamine over a wide range of doses (0.125–4.0 mg/kg IP) on rat unconditioned behaviour were examined in the presence of food and water (experiment 1), in their absence (experiment 2) and after microinjection (2.0 μg in 0.5 μl) directly into the striatum (experiment 3). In experiment 1 very low doses (0.125 and 0.25 mg/kg) stimulated the intake of food, but not water, and higher doses produced locomotor hyperactivity, rearing, stereotyped sniffing and anorexia. In experiment 2 all doses, including very low doses (0.125 and 0.25 mg/kg), significantly potentiated locomotor activity. In experiment 3, microinjection into the corpus striatum elicited substantial feeding, but not drinking, locomotor activity or stereotyped behaviour. The results suggest that a single graded facilitative mechanism underlies the effects on food intake and other behavioural effects of amphetamine, as implied by a general hypothesis of amphetamine action proposed in the literature, and that these effects may to a large extent by mediated by forebrain dopamine systems.
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    URL: http://dx.doi.org/10.1007/BF00433737
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    Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats (1982)
    Springer
    Psychopharmacology 78 (1982), S. 373-376 
    Details
    ISSN: 1432-2072
    Keywords: Phencyclidine ; d-amphetamine ; Lithium ; Locomotor activity ; Stereotyped behaviors ; Ataxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract d-Amphetamine and phencyclidine (PCP) have both been reported to produce manic-like sequela in humans, effects that are reportedly antagonized by lithium. To test the hypothesis that the acute effects of these drugs in rats may serve as models of mania, the behaviors, induced by d-amphetamine (3 mg/kg) or PCP (5 mg/kg) were quantified on behavioral rating scales subsequent to chronic dietary pretreatment with lithium carbonate or control diet. On day 14 of pretreatment, PCP-induced stereotyped behaviors and ataxia were potentiated in rats receiving lithium (plasma levels 1.0±0.23 mEq/l). PCP-induced locomotor activity was not affected by lithium pretreatment. Stereotypies and locomotion induced by d-amphetamine were also not significantly affected by lithium pretreatment. These results suggest that neither PCP nor amphetamine administered acutely to rats will be useful models to explore the manic-like symptoms produced by these drugs in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433745
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    GABAergic mechanisms within the ventral tegmental area: Involvement of dopaminergic (A 10) and non-dopaminergic neurones (1982)
    Springer
    Psychopharmacology 77 (1982), S. 186-192 
    Details
    ISSN: 1432-2072
    Keywords: GABA ; Ventral tegmental area ; Dopamine ; Pictrotoxin ; EOS ; Enkephalin ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The spontaneous activity of rats was measured after activation or inhibition of GABA activity in the ventral tegmental area of the midbrain (VTA). Six hours after bilateral injection of ethanolamine-o-sulphate (GABA agonist) into the VTA, the behavioural activation induced either by d-amphetamine (amph) or by bilateral VTA infusion of a long-lasting enkephalin analogue was completely blocked. Bilateral infusion of picrotoxin (GABA antagonist) into the VTA elicited a short-lived (40 min) dose-dependent behavioural activation which was not reduced either by prior specific lesion of the meso-cortico-limbic dopaminergic neurones or by administration of the opiate antagonist naloxone. Moreover, the simultaneous administration of picrotoxin and amph induced complex changes in behaviour which consisted of additive effects during the first 40 min, followed by an inhibition of the activating effect of amph. Our findings indicate that GABA-mediated inhibition involves both dopaminergic and non-dopaminergic neurones within the VTA, and possible implications for human pathology are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431946
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    The effect of tryptamine on serotonin release from hypothalamic slices is mediated by a cholinergic interneurone (1982)
    Springer
    Psychopharmacology 78 (1982), S. 85-88 
    Details
    ISSN: 1432-2072
    Keywords: Hypothalamus ; Serotonin ; Tryptamine ; Acetylcholine ; Release ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tryptamine produced a concentration-related inhibition of potassium-evoked release of tritium from slices of rat hypothalamus preloaded with 3H-serotonin. This effect of tryptamine was blocked by a series of serotonin antagonists with a relative order of potency which suggested that tryptamine was acting on a post-junctional serotonin receptor. However, the response to tryptamine was also blocked by tetrodotoxin, indicating that tryptamine may be acting indirectly via the release of a second neurotransmitter. The finding that physostigmine enhanced, whilst atropine antagonised the effect of tryptamine suggests that the second neurotransmitter may be acetylcholine. This possibility is discussed.
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    URL: http://dx.doi.org/10.1007/BF00470595
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    3H-imipramine high-affinity binding sites in rat brain. Effects of imipramine and lithium (1982)
    Springer
    Psychopharmacology 77 (1982), S. 94-97 
    Details
    ISSN: 1432-2072
    Keywords: 3H-imipramine binding site ; Imipramine ; Lithium ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The specific high-affinity binding of 3H-imipramine to rat brain membranes was investigated. Five weeks of lithium treatment decreased the number of binding sites, but had no effect on the affinity constants. Long-term imipramine treatment had no effect on the number of binding sites but apparently decreased the affinity. The latter effect was probably due to imipramine remaining in the membrane preparation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00436105
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    Isoprenaline increases brain concentrations of administered l-dopa and l-tryptophan in the rat (1982)
    Springer
    Psychopharmacology 77 (1982), S. 98-100 
    Details
    ISSN: 1432-2072
    Keywords: l-dopa ; Tryptophan ; Brain concentration ; Isoprenaline ; Carrier transport ; Blood-brain barrier ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A small dose of isoprenaline or saline was administered intraperitoneally to rats 20 min before the administration of one of the amino acids l-dopa or l-tryptophan. Isoprenaline caused a marked increase in the brain concentration of the administered amino acid. Isoprenaline has previously been shown to cause a decrease in at least some of those plasma amino acids which compete with l-dopa and tryptophan for carrier-mediated transport into the brain. The effect of isoprenaline on the concentrations of dopa and tryptophan in the brain is suggested to be at least partly caused by a change in the relationship between endogeneous and administered amino acids. It is also possible that a direct effect of isoprenaline on the blood-brain barrier transport system contributes to the effect. The reported finding might be of clinical interest in view of the therapeutic importance of aromatic amino acids with a central site of action.
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    URL: http://dx.doi.org/10.1007/BF00436106
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  • 189
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    Residual effects of prolonged cannabis administration on exploration and DRL performance in rats (1982)
    Springer
    Psychopharmacology 77 (1982), S. 124-128 
    Details
    ISSN: 1432-2072
    Keywords: Chronic cannabis ; Locomotor activity ; DRL performance ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic oral administration of cannabis extract to rats (daily Δ 9 dose 20 mg/kg) was examined for its residual effect on open field activity and DRL (differential reinforcement of low-rate responding) performance, following a 2–3-month drug-free period. Locomotor activity during the latter part of an open field test was markedly increased in rats previously treated for either 6 months or 3 months with the drug. The same treatments also produced a significant impairment on a DRL-20 task relative to control subjects' performance. These and other findings (impaired maze learning and facilitated two-way shuttle box avoidance) might mean that cannabis produces long-lasting hippocampal, dysfunction in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431933
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    Learning impairment in the radial-arm maze following prolonged cannabis treatment in rats (1982)
    Springer
    Psychopharmacology 77 (1982), S. 117-123 
    Details
    ISSN: 1432-2072
    Keywords: Chronic cannabis ; Learning ; Radial-arm maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic oral administration of cannabis extract to rats (daily Δ 9tetrahydrocannabinol dose 20 mg/kg) was examined in three experiments for its residual effect on radialarm maze learning following a 1-month drug-free period. Learning a simple eight-arm maze was significantly impaired in rats treated for either 6 months (Experiment I) or 3 months (Experiment II) with the drug. In Experiment III, animals that received the extract for 3 months exhibited significant learning deficits on a much more difficult 12-arm radial maze. The results demonstrate that the deleterious effects of cannabis on radial-arm maze learning are probably due to a tendency toward increased vigilance and perseveration, possibly combined with an impaired utilization of spatial cues.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431932
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    Oral dyskinesia in rats following brain lesions and neuroleptic drug administration (1982)
    Springer
    Psychopharmacology 77 (1982), S. 134-139 
    Details
    ISSN: 1432-2072
    Keywords: Animal model ; Rat ; Tardive dyskinesia ; Oral dyskinesia ; Chronic haloperidol ; Neuroleptic ; 6-Hydroxydopamine ; Kainic acid ; Frontal cortex ; Striatum
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract After 10–12 weeks of chronic haloperidol administration rats with frontal cortex ablations or lesions induced by intracerebroventricular injection of 6-hydroxydopamine developed vacuous chewing behavior at a fairly stable frequency (bifrontal ablations had 15–20, 6-hydroxy-dopamine lesioned rats 7–12 chewing movements/min). This behavior persisted for 10 weeks after the last injection of haloperidol decanoate. However, rats with frontal cortex lesions developed a low rate of vacuous chewings (4–8 chewings/min) even without haloperidol administration. Bilateral intrastriatal injections of kainic acid in combination with chronic haloperidol administration did not cause chewing movements in excess of unlesioned haloperidol-treated controls. Pharmacological tests of this animal model for tardive dyskinesia (TD) revealed similarities to human TD, but also differences. Dopamine agonists (apomorphine) and antagonists (haloperidol) both lowered chewing behavior analogous to reported effects on TD and so did gabaculine. The cholinergic drugs physostigmine and pilocarpine, however, increased chewing in rats, while anticholinergics (atropine) reduced it, in contrast to reported effects on human TD.
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    URL: http://dx.doi.org/10.1007/BF00431935
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    Locomotor activity of rats after stimulation of the nucleus locus coeruleus region or after lesion of the dorsal noradrenergic bundle: Effects of clonidine, prazosin and yohimbine (1982)
    Springer
    Psychopharmacology 78 (1982), S. 239-244 
    Details
    ISSN: 1432-2072
    Keywords: Locus coeruleus ; Dorsal noradrenergic bundle ; Open-field ; Clonidine ; Prazosin ; Yohimbine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We previously showed in the rat that electrical stimulation of the nucleus locus coeruleus produced, 4 weeks later, a significant increase in the number of α1 and α1 in the cerebral cortex. In a parallel pharmacological study, we tested the effects of small doses of clonidine on the locomotor activity of stimulated rats and implanted but not stimulated animals. In stimulated rats only, clonidine had a dual effect: firstly, sedation 30 min after injection, and secondly, hyperactivity which was observed 24 h after injection. In the present study, using the same behavioral paradigm, we tested the effects of small doses of clonidine on the locomotor activity of three groups of rats: stimulated in the locus coeruleus, lesioned in the dorsal noradrenergic bundle and controls. In stimulated rats injected with clonidine, delayed hyperactivity appeared 24 h after the injection, beginning at the smallest dose used (2.5 μg/kg). This hyperactivity was not due to the stimulation per se, since it did not appear in stimulated rats injected with the vehicle. In rats with dorsal noradrenergic bundle lesions, this delayed hyperactivity was observed only after a high dose (50 μg/kg) of clonidine. In a second experiment, we tested the effect of small doses of prazosin or of yohimbine on the delayed, drug-induced, hyperactivity of stimulated or lesioned rats. In stimulated rats, prazosin (an α1-adrenoceptor antagonist) suppressed the hyperactivity produced by clonidine. Yohimbine (an α2-adrenoceptor antagonist) markedly increased the locomotor activity of stimulated rats injected with vehicle. Likewise, in lesioned rats, prazosin suppressed the hyperactivity produced by a dose of 50 μg/kg of clonidine. These results are interpreted in relation to the possible role of α-adrenoceptors in the regulation of locomotor activity.
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    URL: http://dx.doi.org/10.1007/BF00428158
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    Antagonism of the anticonflict effects of chlordiazepoxide by β-carboline carboxylic acid ethyl ester, Ro 15-1788 and ACTH(4–10) (1982)
    Springer
    Psychopharmacology 78 (1982), S. 256-260 
    Details
    ISSN: 1432-2072
    Keywords: Anxiety ; Punishment ; Conflict ; Chlordiazepoxide ; β-Carboline carboxylic acid ethyl ester ; Ro 15-1788 ; ACTH(4–10) ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antagonism of the anticonflict effect of chlordiazepoxide (CDP) by β-carboline carboxylic acid ethyl ester (BCCE), Ro 15-1788 and ACTH(4–10) has been evaluated in the Geller-Seifter rat conflict test in which CDP increases punished (conflict), but not unpunished responding. BCCE (0.5–10 μg ICV) produced a dose-dependent reduction in the anticonflict activity of CDP. This was also significantly reduced by Ro 15-1788 (25 mg/kg IP) and a high dose of ACTH(4–10) (5 μg ICV). None of these test compounds had a marked direct effect on punished or unpunished responding in the doses used. These experiments provide further physiological support for the suggestion from binding studies that BCCE and Ro 15-1788 act on benzodiazepine receptors. However, the ability of ACTH(4–10) to reduce the anticonflict effect of CDP may be by some other, possibly opioid, mechanism.
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    URL: http://dx.doi.org/10.1007/BF00428161
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    Benzodiazepine antagonist Ro 15-1788: Neurological and behavioral effects (1982)
    Springer
    Psychopharmacology 78 (1982), S. 8-18 
    Details
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Benzodiazepine antagonist ; Ro 15-1788 ; Barbiturates ; Depressants ; Competitive antagonism ; Mouse ; Rat ; Dog ; Squirrel monkey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In neurological and behavioral studies in mice, rats, dogs and squirrel monkeys, the imidazobenzodiazepinone Ro 15-1788 acted as a potent benzodiazepine antagonist. The antagonistic activity was both preventive and curative and seen at doses at which no intrinsic effects were detected. It was highly selective in that it acted against CNS effects induced by benzodiazepines but not against those produced by other depressants, such as phenobarbitone, meprobamate, ethanol, and valproate. The onset of action was rapid even after oral administration. Depending on the animal species studied, the antagonistic effects lasted from a few hours to 1 day. The acute and subacute toxicity of Ro 15-1788 was found to be very low. Benzodiazepine-like effects were not seen.
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    URL: http://dx.doi.org/10.1007/BF00470579
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    A quantitative study in the rat on the relationship between imipramine levels in brain and serum (1982)
    Springer
    Psychopharmacology 76 (1982), S. 48-51 
    Details
    ISSN: 1432-2072
    Keywords: Imipramine ; Serum levels of IMI ; Brain levels of IMI ; Tricyclic antidepressants ; Compartmentation of IMI ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum and brain levels of the tricyclic antidepressant drug imipramine (IMI) were studied in the rat under a variety of conditions. IV doses (range 1 nmol kg-1 to 15 μmol kg-1, 350 ng–5mg kg-1) and administered 5 min before death, were linearly correlated with IMI levels in serum, frontal cortex, and cerebellum. In this experiment, the highest levels of IMI were achieved in the frontal and occipital cortex and the lowest levels were found in the brain stem. The regional distribution was more even in rats pretreated with thiopental or γ-hydroxybutyric acid, drugs that alter cerebral blood flow. After 20 min or more, tracer amounts of IMI injected IV to IMI-pretreated rats [1 or 17 days, daily dose 2×36 μmol kg-1 (10 mg kg-1), last dose 89 μmol kg-1 (25 mg kg-1), 2–3 h before death] exhibited a distribution pattern in serum and various brain regions similar to that of the unlabeled drug. In the latter experiments, content (per volume) of the tracer or unlabeled IMI was more than 25-fold higher in various brain areas than in serum. It is concluded that despite large differences in drug levels in serum or brain, a close relationship is maintained under the conditions studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430754
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  • 196
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    THIP inhibits feeding behavior in fasted rats (1982)
    Springer
    Psychopharmacology 76 (1982), S. 75-78 
    Details
    ISSN: 1432-2072
    Keywords: THIP ; GABA ; d-Amphetamine ; Feeding behavior ; Anorexigenic agents ; GABA-receptor ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridin-3-ol (THIP) were compared with those of d-amphetamine and GABA in fasted rats. Intravenously-administered THIP produced a dose-dependent decrease in food consumption (ED50≃1.5 mg/kg) by an action that was not reversed by prior subcutaneous or simultaneous intravenous (IV) injection of bicuculline. d-Amphetamine-SO4 also produced a decrease in food consumption in this model (ED50≃0.2 mg/kg, IV). Unlike THIP, GABA (in doses up to 100 mg/kg, IV) did not produce a marked anorexigenic effect. These results provide further evidence that THIP can penetrate the “blood-brain barrier”, and that central GABA-ergic systems are involved in controlling food intake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430760
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  • 197
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    The role of fentanyl training dose and of the alternative stimulus condition in drug generalization (1982)
    Springer
    Psychopharmacology 76 (1982), S. 149-156 
    Details
    ISSN: 1432-2072
    Keywords: Drug discrimination ; Drug generalization ; Fentanyl ; Morphine ; Amphetamine ; Nicotine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Different groups of rats were trained to discriminate fentanyl (F) (0.03, 0.02, or 0.01 mg/kg) from saline or to discriminate 0.03 mg/kg fentanyl (F) from alternative stimulus conditions (saline, 0.15 mg/kg nicotine, or 0.01 mg/kg F). When percentage of responses on the drug lever and percentage of time spent responding on the drug lever were used as dependent variables, it was found that training dose and alternative stimulus condition both affected the ED50 and the slope of the F generalization gradient. ED50 and slope values based on group data were not significantly different from values based on individual data. Differences between the results of the first and second 2.5-min period of the extinction test were not significant. ED50 and slope values were unaffected by the preceding training session, except in the group trained to discriminate 0.03 from 0.01 mg/kg F. A lever selection measure showed a significant effect of alternative stimulus condition on ED50 values only. Training dose and alternative stimulus condition also affected the generalization to morphine. Under none of the conditions explored in this study did generalization occur to amphetamine or nicotine. The results are discussed in terms of the relative nature of drug generalization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00435269
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  • 198
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    Differences in the effects of d-fenfluramine and morphine on various responses of rats to painful stimuli (1982)
    Springer
    Psychopharmacology 76 (1982), S. 188-192 
    Details
    ISSN: 1432-2072
    Keywords: d-Fenfluramine ; Morphine ; Brain serotonin ; Nociception ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of d-fenfluramine and morphine on various nociceptive responses of rats were investigated. Unlike morphine, which inhibited all the responses examined, d-fenfluramine inhibited jumping and paw licking of rats on a hot plate, but did not increase the latency of tail withdrawal from hot water. The effects of d-fenfluramine on both responses on the hot plate were prevented by pretreatment with metergoline, a serotonin antagonist, whereas this pretreatment only reduced the effect of morphine on paw licking. The inhibition of tail withdrawal by morphine was also significantly reduced by metergoline treatment. The results confirm previous findings suggesting a role of serotonin in the mechanism by which morphine inhibits some nociceptive responses in rats. They also show that d-fenfluramine, a selective releaser and uptake inhibitor of serotonin at nerve endings, does not completely reproduce the antinociceptive effects of morphine in this species.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00435276
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  • 199
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    Increased food intake following the manipulation of intracerebral dopamine levels with gamma-hydroxybutyrate (1982)
    Springer
    Psychopharmacology 76 (1982), S. 273-277 
    Details
    ISSN: 1432-2072
    Keywords: Gamma-hydroxybutyric acid ; Dopamine ; Stereotyped behaviour ; Food intake ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The administration of gamma-hydroxybutyric acid (GHB) initially causes a temporary “sleep-like” state during which there is an increase in forebrain dopamine levels. The present series of experiments examined whether in the period following the GHB-induced behavioural depression, when accumulated dopamine is dispersed, there is any behavioural evidence of increased dopaminergic activity. The first experiment, in which GHB was injected directly into the cerebral ventricles, demonstrated that in the immediate post-recovery period rats exhibited various forms of stereotyped oral behaviour and stereotyped sniffing. Unexpectedly, it was also observed that if food were present animals preferred to eat. The nature of this feeding response was examined in two further experiments. Firstly, it was shown that in the period following the behavioural depression animals would perform, in a dose-dependent fashion, an operant response which was rewarded by food. Secondly, the GHB-induced increase in feeding was abolished by the pre-treatment of animals with either the dopamine synthesis inhibitor alpha-methyl-p-tyrosine, or the dopamine receptor blocker haloperidol. These data indicate that (i) in the period when it is known that the GHB-induced accumulation of dopamine is dispersing, there is behavioural evidence of increased dopaminergic activity; (ii) the feeding response is not a simple oral reflex; and (iii) in addition to being essential for food intake dopaminergic transmission may play a direct role in the production of feeding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432560
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  • 200
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    DSP4-induced two-way active avoidance impairment in rats: Involvement of central and not peripheral noradrenaline depletion (1982)
    Springer
    Psychopharmacology 76 (1982), S. 303-309 
    Details
    ISSN: 1432-2072
    Keywords: Systemic DSP4 ; Two-way avoidance ; Acquisition ; Spontaneous activity ; NA uptake ; Endogenous NA ; Peripheral NA ; Pain sensitivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following adminsitration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2×30 mg/kg IP) was not found to cause any avoidance impairment, althogh its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance asquisition is mediated via central, and not peripheral NA neurons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00449115
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