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  • 1990-1994  (1,274)
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  • 101
    ISSN: 1432-1106
    Keywords: Periaqueductal gray ; Stress ; Defense Passive coping behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Much evidence suggests that the midbrain periaqueductal gray region (PAG) plays a pivotal role in mediating an animal's responses to threatening, stressful, or painful stimuli. Active defensive reactions, hypertension, tachycardia and tachypnea are coordinated by a longitudinally oriented column of cells, found lateral to the midbrain aqueduct, in the caudal two-thirds of the PAG. In contrast, microinjections of excitatory amino acid (EAA) made in the ventrolateral region of the PAG in anesthetized or isolated animals evoke hypotension, bradycardia, and behavioral arrest. The aim of the present study was to examine further the effects of activation of neurons in the ventrolateral PAG. By injecting into this region low doses (40 pmol) of kainic acid (KA), a long-acting EAA, it was possible to observe a freely moving rat's behavior in a social situation (i.e., paired with a weight-matched, untreated partner). Such injected rats become quiescent, i.e., there was a cessation of all ongoing spontaneous activity. These rats were also hyporeactive: the investigative approaches of the partner failed to evoke orientation, startle reactions, or vocalization. Electroencephalographic measurements indicated that the effects of injections of KA in the ventrolateral PAG were not secondary to seizure activity. In addition to the quiescence and hyporeactivity reported here, and the hypotension and bradycardia reported previously, the ventrolateral PAG is a part of the brain from which analgesia has been readily evoked by electrical stimulation, or microinjections of either EAA or morphine. As a reaction to “deep” or “inescapable” pain, chronic injury, or defeat, animals often reduce their somatomotor activity, become more solitary, and are generally much less responsive to their environment. These data, and those from other recent studies, suggest that neurons in the ventrolateral PAG may play an important role in integrating such a passive behavioral response of which quiescence and hyporeactivity are the major components.
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  • 102
    ISSN: 1432-1084
    Keywords: Brain oedema ; Dehydration ; Magnetic resonance imaging ; Middle cerebral artery occlusion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mannitol and furosemide treatment of ischaemic brain oedema caused by middle cerebral artery occlusion (MCAO) was studied by MRI in 87 rats. MRI was performed in all rats before and 30–360 min after drug infusion. The examinations were performed in the presence of an intact blood-brain barrier (BBB) 6 h after MCAO, and 3 days after MCAO at the time of maximal disruption of the BBB. Spin echo (SE) sequences were used for imaging and for determination of the relaxation times T1 and T2. Subtraction images were constructed. Furosemide dehydrated healthy and ischaemic brain. Mannitol had no dehydrating effect on healthy brain tissue. However, when the BBB was disrupted in severe oedema mannitol produced a decrease in water content, a shortening of T1 and T2, and a decrease in intracranial pressure (ICP), while in less severe oedema mannitol could increase brain water content, thus aggravating ICP. The subtraction technique allowed visualisation of the transient change in bulk in water animals with disruption of the BBB after mannitol treatment.
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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 102 (1994), S. 165-170 
    ISSN: 1432-1106
    Keywords: Norepinephrine ; Neuromodulation ; Long-term potentiation ; Cerebellar-hippocampal interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vitro norepinephrine (NE) induces both short and long-term β-receptor-mediated potentiation of the perforant path-evoked population spike in the dentate gyrus. NE or locus coeruleus (LC) activation in vivo also produces a β-receptor dependent potentiation of population spike amplitude in anesthetized rat. Studies of behavioral state modulation of population spike amplitude in awake rats, and in rats depleted of NE, however, have led to the hypothesis that LC-NE activation should act to suppress or reduce population spike amplitude in the dentate gyrus of unanesthetized rat. Using glutamate activation of LC in awake unrestrained rats (n=12), the present study provides evidence that LC activation in the awake rat does not reduce, but potentiates, population spike amplitude. The potentiation effect was long-lasting (〉25min) in 50% of the experiments. In addition glutamate ejections in the third lobe of cerebellar rostral vermis produced potentiation of population spike amplitude (n=3) and population excitatory postsynaptic potential slope. Ejections at sites outside the LC and rostral vermis were ineffective (n=5). Behavioral effects of glutamate ejection did not predict the occurrence of potentiation. These data support the hypothesis that phasic activation of LC cells is likely to induce short-term, and possibly long-term, potentiation of dentate gyrus throughput in alert animals.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 100 (1994), S. 67-84 
    ISSN: 1432-1106
    Keywords: Cerebral cortex ; Anatomy ; Connections Corticocortical ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Tel, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.
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  • 105
    ISSN: 1432-1106
    Keywords: Cerebellum ; Plateau ; Facial ; Crus IIa Guinea pig ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We obtained intracellular recordings of 84 Purkinje cells in vitro from guinea pig slices and of 35 cells in vivo from ketamine-anesthetized rats in order to assess detailed properties of synaptic responses in Purkinje cells following granule cell activation. In vitro, electrical stimulation of the granule cell layer underlying recorded Purkinje cells was used in sagittal slices to predominantly activate synapses on ascending granule cell axons. In vivo, stimulation of the upper lip was used to activate Purkinje cells overlying the upper lip patch in the granule cell layer of crus IIa. In the presence of a GABAA antagonist, Purkinje cells at resting membrane potential responded to both electrical stimulation in vitro and peripheral stimulation in vivo, with a depolarization of 1–10 mV amplitude that lasted for 100–300 ms in the absence of climbing fiber input. Similar prolonged depolarizations could also be induced by brief depolarizing current pulses delivered through the recording electrode, demonstrating that either synaptic or direct depolarization may activate inward currents leading to a sustained response. In support of this hypothesis we found that prolonged depolarizations were shortened significantly when stimulation in the granule cell layer or intracellular current pulses were delivered during hyperpolarizing current steps. Stimulation in the granule cell layer or intracellular current pulses delivered during periods of spontaneous somatic spiking resulted in prolonged depolarizations in dendritic recordings, which were accompanied by an increase in somatic spiking frequency. Following upper lip stimulation in vivo, this increase in somatic spiking was interrupted by an inhibition of 10–50 ms duration. In a majority of recordings, this inhibition did not completely abolish prolonged depolarizations, however, and a delayed increase in somatic spike frequency was still observed. These results suggest that prolonged increases in Purkinje cell spike frequency following peripheral stimulation are due to an underlying prolonged dendritic depolarization induced by granule cell input. Further, a single, short burst of input via ascending granule cell axons appears to be sufficient to induce these responses.
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  • 106
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 100 (1994), S. 239-249 
    ISSN: 1432-1106
    Keywords: Neostriatum ; In vitro brain slices Inward rectification ; Subthreshold ion conductances Firing pattern ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intracellular recordings from slice preparations were used to assess the subthreshold electrophysiological behavior of rat neostriatal projection neurons. Both current steps and ramp currents were used to estimate the current-voltage relationship (I–V plot). Inward rectification in the subthreshold range was a characteristic of most neurons. The amount of rectification varied greatly, and it was complex: membrane voltage trajectories in response to ramps were made up by almost piecewise changes in the rate of voltage rise, suggesting that multiple conductances contribute to the subthreshold range. Inward current blockers such as tetrodotoxin (TTX) or Cd2+ decreased inward rectification, whereas outward current blockers such as tetraethylammonium (TEA) or 4-aminopyridine (4-AP) increased inward rectification. However, most inward rectification was due to TEA- and Cs+-sensitive conductances and not to TTX- or Cd2+-sensitive conductances. Cs+-sensitive conductances predominated at more negative membrane potentials, whereas 4-AP-sensitive conductances predominated at just ±10 mV below the firing threshold. In spite of a very slow activation, there was evidence for transient outward currents modulating the response, i.e., 4-AP-sensitivity, and voltage-sensitivity for firing frequency and threshold. TEA-sensitive conductances also contributed toward fixing the firing threshold. These results imply the contribution of various ion conductances on the shaping of the characteristic physiological firing recorded in vivo. Modulation of these responses by transmitters or peptides may help to understand neural processing in the neostriatum.
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  • 107
    ISSN: 1432-1106
    Keywords: Transplantation ; Serotonin neurons ; Hypothalamus ; Electron microscopy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have previously reported that a cell suspension from the rostral part of the embryonic raphe grafted to the basal hypothalamus of 5,7-dihydroxytryptamine-denervated rats produced incomplete serotonin (5-HT) re-innervation of the suprachiasmatic nucleus (SCN) as opposed to hyper-innervation of the supraoptic nucleus (SON). We took advantage of this experimental model to investigate whether the graft-derived, 5-HT fibres retained normal ultrastructural features, and, particularly, a normal density of synaptic junctions, irrespective of the extent of target re-innervation. The intrinsic features of immunostained, graft-derived 5-HT axonal varicosities in both the SCN (ventral portion) and the SON were essentially similar to those exhibited by the respective endogenous innervation. Analysis of well-preserved varicosities in uninterrupted series of thin sections allowed us to evaluate directly the proportions of junctional to non-junctional 5-HT varicosities in both regions. Synaptic incidences were also remarkably conserved after grafting (45.5% in the SCN versus 38.5% in the SON; 48% and 38% in normal rats, respectively). Synapses were primarily reestablished on dendritic shafts, which also were identified as the major post-synaptic targets of the normal 5-HT innervations. We noted, however, a tendency toward increased numbers of symmetrical versus asymmetrical synapses in both the SCN and SON of grafted rats. Thus, irrespective of whether hypo-or hyper-innervation patterns developed post-grafting, the transplanted 5-HT neurons essentially retained normal ultrastructural features in their target territories, with a normal incidence of synaptic junctions. The data provide further support to the hypothesis that the innervation territory is the major determinant of the frequency with which ingrowing 5-HT fibres make synaptic junctions.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 101 (1994), S. 365-374 
    ISSN: 1432-1106
    Keywords: 6-Hydroxydopamine ; Ibotenic acid ; Rotation ; Amphetamine ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lesions of the dopaminergic nigrostriatal tract produce a range of motor and sensorimotor deficits. One of the simplest and most reliable is the rotational response of the animal following activation with drugs that stimulate the dopaminergic network, most notably amphetamine and apomorphine. Consequently, the rotation test has been extensively used in assessing the success of treatments designed to restore dopaminergic function, including neural transplants. The present study investigates whether rotation induced by 6-hydroxydopamine lesions of the nigrostriatal bundle in rats is modified by additional lesions in the neostriatum. It was found that apomorphine-induced rotation can be reduced by ibotenic acid lesions of the dopamine-deafferented striatum, and that the extent of the reduction was proportional to the size of the lesions. In contrast, such lesions produced a non-significant reduction in amphetamine-induced rotation, although the correlation between the extent of the reduction and the size of the lesion was again apparent. Since the pattern of change was similar in direction, albeit smaller in magnitude, than the previously reported effects of intrastriatal transplantation in rats with similar nigrostriatal lesions, rotation tests alone do not provide an unequivocal test of graft survival and function.
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  • 109
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 101 (1994), S. 427-438 
    ISSN: 1432-1106
    Keywords: Facial motor nucleus ; Reticular formation ; Biocytin ; Cholera toxin B ; Synapses ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to determine whether neurones in the parvicellular reticular formation are in direct synaptic contact with motoneurones innervating facial muscles, a combined retrograde and anterograde transport study was carried out in the rat. Animals received injections of the retrograde tracer cholera toxin B conjugated to horseradish peroxidase into facial muscles and of the anterograde tracer biocytin into the parvicellular reticular formation. The facial motor nucleus was then examined for anterograde and retrograde labelling in the light and electron microscopes. Retrogradely labelled neurones were found in the facial motor nucleus with a distribution that was dependent on the muscles injected. Terminals anterogradely labelled with biocytin from the parvicellular reticular formation were observed in the motor nucleus amongst the retrogradely labelled neurones. At the electron microscope, the retrogradely labelled cells were found to receive input from unlabelled terminals and from terminals that were anterogradely labelled from the injections of biocytin in the parvicellular reticular formation. The labelled terminals were 1–2 μm in diameter at the active zone and packed with spherical vesicles. They formed both symmetrical and asymmetrical synapses with their labelled or unlabelled targets. It is concluded that neurones in the parvicellular reticular formation form direct synaptic contact with motoneurones of facial muslces. This may represent a pathway by which the basal ganglia can directly influence orofacial movement, as the substantia nigra is known to project to that part of the reticular formation.
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  • 110
    ISSN: 1432-1106
    Keywords: Estrogen ; Gastric acid secretion ; Glucose ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gastric acid outputs caused by glucose injection into the lateral hypothalamic area (LHA) were examined in insulin hypoglycemia with or without estradiol-17β (EST) administration in bilaterally ovariectomized (OV) female rats. The basal level of acid output was higher in OV rats without EST than in OV rats with EST. When acid response was expressed as the percentage change, glucose injection into the LHA decreased acid output in a dose-dependent fashion in OV rats, while, in OV rats with EST, glucose injection into the LHA also reduced acid output without dose dependency. It was also noted that the threshold concentration of glucose that induced an acid response was lower in OV rats without EST than in OV rats with EST. These findings suggest that glucose-sensitive neurons responsible for gastric acid secretion can be modulated by estrogen at the LHA level.
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  • 111
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 100 (1994), S. 170-174 
    ISSN: 1432-1106
    Keywords: Withdrawal reflexes ; Motion analysis Nociception ; Pain ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To use sensory information from the skin to guide motor behaviour the central nervous system must transform sensory coordinates into movement coordinates. As yet, the basic principles of this crucial neural computation are unclear. One motor system suitable as a model for the study of such transformations is the spinal withdrawal reflex system. The spatial organization of the cutaneous input to these reflexes has been characterized, and we now introduce a novel method of motion analysis permitting a quantitative analysis of the spatial input-output relationship in this motor system. For each muscle studied, a “mirror-image” relationship was found between the spatial distribution of reflex gain for cutaneous input and the pattern of cutaneous unloading ensuing on contraction. Thus, there is an “imprint” of the movement pattern on this motor system permitting effective sensorimotor transformation. This imprint may indicate the presence of a learning process which utilizes the sensory feedback ensuing on muscle contraction.
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  • 112
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 101 (1994), S. 297-306 
    ISSN: 1432-1106
    Keywords: GABA receptors ; Benzodiazepine receptors ; Stress ; Corticosterone ; Sex differences ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since many hormonal indices of stress responsiveness are sexually dimorphic in rats, we examined sex differences and the effects of gonadectomy on the stress-related changes in GABAA/benzodiazepine receptors in rats. Intact or ovariectomized female rats displayed a markedly greater corticosterone response and a more pronounced increase in benzodiazepine receptors than males (intact or orchidectomized) after acute handling or swim stress. Swim stress increased benzodiazepine receptor density without modifying affinity in cortex, hippocampus, and hypothalamus. Corticosterone treatment induced benzodiazepine receptor levels comparable to those seen after swim stress in all hormone groups. Handling stress also enhanced cortical low-affinity GABAA receptor levels in males and ovariectomized females. Both GABA and benzodiazepine receptor levels were positively correlated with circulating corticosterone levels in female, but not male, groups. GABA/benzodiazepine coupling was unaffected by stress or hormonal status. These sexual dimorphisms in hormonal responses to stress may help elucidate the causes and consequences of stress-induced changes in the GABAA/benzodiazepine receptor complex.
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  • 113
    ISSN: 1432-1106
    Keywords: Platelet-derived growth factor ; Striatal neurons ; DARPP-32 ; Huntington's disease ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of the present study was to determine if either of the two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, exerts trophic effects in vitro on developing rat striatal neurons. Striatal neurons were identified using immunocytochemistry for dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein with a molecular weight of 32 kilodalton (DARPP-32). In control cultures without PDGF, the mean number of DARPP-32-positive neurons decreased by 47% at days 3 to 5 in vitro. PDGF-BB, but not PDGF-AA, significantly increased the number of DARPP-32-positive neurons both at day 3 (by 42%) and day 5 (by 149%). Total cell number was similar in control and PDGF BB-treated cultures, suggesting that, in striatal cultures, the action of PDGF-BB is relatively specific for DARPP-32-positive neurons. The DARPP-32-positive neurons in PDGF-BB-treated cultures had longer neurites and larger soma areas than those in control and in PDGF-AA-treated cultures. Our data provide evidence that PDGF-BB exerts a trophic action on striatal DARPP-32-positive neurons in vitro by promoting cell survival and morphological differentiation, although a stimulatory effect on intraneuronal DARPP-32 levels also is possible. The findings raise the possibility that PDGF-BB might also be involved in the development and maintenance of striatal neurons in vivo, and could be used to counteract striatal degeneration in models of Huntington's disease.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 102 (1994), S. 21-33 
    ISSN: 1432-1106
    Keywords: Somatosensory ; Acetylcholine ; Alzheimer's disease ; Nucleus basalis magnocellularis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cholinergic neurons in the nucleus basalis magnocellularis (NBM) project to the cerebral cortex and are thought to play an important role in learning and memory, and other cognitive functions. In the present study, we examined the effects of NBM stimulation on the response properties of individual cortical neurons in layer V of the rat somatosensory cortex. Seventy-three neurons were studied before and after a brief electrical stimulation of NBM. Transient changes in spontaneous activity were observed in 60% of the cells, and in most cases this background activity decreased. Recordings lasting more than 1 h stimulation were obtained from 56 cells. Because some NBM stimulation-induced effects lasted several hours, neurons were evaluated in two groups, NBM1 and NBM2. NBM1 neurons were those exposed to either the first NBM stimulation of the day or an NBM restimulation following a more than 5 h stimulation-free period. Neurons exposed to NBM restimulation following a stimulation free interval of less than 5 h were classified as NBM2. Sixty-nine percent of the 32 NBM1 neurons displayed marked decreases in spontaneous activity and/or increases in the response evoked by deflecting a contralateral facial vibrissa. NBM1 stimulation caused some units to respond to previously minimally effective whisker stimuli. Stimulation effects often lasted several hours. By contrast, long-lasting changes were observed in only 25% of the 24 NBM2 neurons, and the only consistent effect was on spontaneous, not stimulus-evoked, activity. Systemic injection of atropine blocked NBM stimulation-induced changes in spontaneous and stimulus-evoked activities. Control neurons, studied without NBM stimulation, failed to display consistent alterations in their response properties during the course of 1 h or more. Results demonstrate that NBM activation produces long-lasting, cholinergically mediated alterations in the response properties of somatosensory cortical neurons. Effects were complex, being influenced by factors such as the time interval between successive stimulations during an experiment. The complexity of these NBM mediated effects should be considered when designing therapies for neurodegenerative disorders characterized by loss of NBM neurons.
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  • 115
    ISSN: 1432-1106
    Keywords: Dopamine ; Striatum ; Ventral mesencephalic grafts ; Voltammetry ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An in vivo voltammetric technique was used to monitor dopamine (DA) release in the 6-hydroxydopamine (6-OHDA)-lesioned rat striatum reinnervated by grafts of ventral mesencephalon containing DA neurons. Extracellular levels of DA were measured during the administration of D1 or D2 DA receptor antagonists. In addition, changes in DA levels induced by agonists and antagonists of excitatory amino acid (EAA) receptors were studied to verify the possible existence of a host glutamatergic control on the grafted DA cells in the ‘transplanted’ rats. Two months after the grafts were performed, the voltammetric signal measured under baseline conditions in the grafted striata was found to be almost similar to that recorded on the contralateral control side. Likewise, in another group of transplanted rats, the turnover of the amine, as expressed by the DOPAC/DA tissue level ratio, was found to have become “normalized” after grafting, compared with the lesion-only group. The increase in the voltammetric signal observed after administering the D2 antagonist sulpiride (100 mg/kg i.p.) was lower in the grafted striata than on the contralateral side, however. This suggests that some D2 autoreceptor subsensitivity may have helped to maintain the baseline level of dopaminergic transmission. Adaptive processes of this kind might compensate for the partial DA reinnervation of the host striatum found to occur on the basis of the tyrosine hydroxylase immunostaining patterns. After administration of either the D1 antagonist SCH 23390 (0.1 mg/kg s.c.), or injection of EAA receptor agonists-1-glutamate, quisqualate and N-methyl-d-aspartate (all 10 nmol i.c.v.) — and antagonists — amino-phosphono-valeric acid (10 nmol i.c.v.) and dizocilpine (MK801, 0.2 mg/kg i.p.) — no significant differences between the two striata were detected in the voltammetric signals. These results suggest that, in the grafted rats, neurons belonging to the host population, such as the striatal cells bearing D1 receptors or the corticostriatal afferents presumed to contain glutamate, might modulate the DA levels, as was found to occur under normal conditions.
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  • 116
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    Experimental brain research 102 (1994), S. 69-74 
    ISSN: 1432-1106
    Keywords: Motoneurone ; Recruitment ; Force modulation ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the context of an analysis concerning factors of importance for the relative contributions of recruitment and rate gradation of muscle force, the distribution of electrical excitability was analyzed for medial gastrocnemius (MG) motoneurones of rat and cat. The experimental data came from previously collected intracellular measurements in animals anaesthetized with pentobarbitone. Electrical excitability was measured as the threshold (nanoamperes) for single spike generation (rheobase) in rat and for maintained repetitive firing (rhythmic threshold) in cat. Furthermore, the data included measurements of axonal conduction velocity and of contractile properties of the muscle units innervated by the studied motoneurones. The units were categorized into types S (slow-twitch, fatigue-resistant), FR (fast-twitch, fatigue-resistant) and FF (fast-twitch, fatiguable) on the basis of the combined criteria of twitch-speed and sensitivity to fatigue. We confirmed that, in spite of the presence of normal-looking symmetrical distributions of axonal conduction velocity, there was a positive skew in the distribution of electrical excitability (relatively high numbers of cells with low thresholds, few with high ones). Within each unit category (S, FR, FF), we ranked the motoneurones according to their relative electrical excitability and calculated the threshold difference between consecutive cells (“threshold spacing”). In accordance with the skewed distribution of electrical excitability, we found that the mean threshold spacing was ranked in the same way as the mean thresholds, i.e. S〈FR〈FF; the statistical analysis showed that, for cats as well as rats, small threshold-spacing steps were significantly more common for S than for FF motoneurones. In the discussion it is pointed out that the narrow threshold-spacing for S units, as compared to FF units, would tend to decrease the relative amount of recruitment-parallel rate modulation in these cells. Thus, the spacing of recruitment thresholds tends to allow the easily recruited S motoneurones to remain firing at relatively low rates during ongoing recruitment gradation, which would be of potential value in promoting a high degree of endurance for long-lasting postural contractions.
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  • 117
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    Archives of microbiology 162 (1994), S. 267-271 
    ISSN: 1432-072X
    Keywords: Key words     Extremely thermophilic eubacterium ; Calderobacterium hydrogenophilium ; Ultrastructure ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract       Calderobacterium hydrogenophilum is an extreme thermophilic, obligately chemoautotrophic, hydrogen-oxidizing bacterium. The cells were shown to be non-motile straight rods of average size 0.4 × 2.5 μm. After negative-staining of the whole cells, no flagella were observed. The multilayered cell wall was of type 1 and possessed a crystalline proteinaceous surface layer exhibiting p4 symmetry. The square unit cells had a lattice constant of approximately 11 nm. Cell division occurred by a constriction mechanism. C. hydrogenophilum differred from a similar hydrogen-oxidizing eubacterium, Hydrogenobacter thermophilus, by the absence of intracytoplasmic membrane structures in chemically fixed cells. However, an electron-dense intracytoplasmic hemispherical structure adhering to the inner membrane was frequently observed.
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  • 118
    ISSN: 1432-2072
    Keywords: Heroin self-administration ; Rat ; 5-HT ; 2-HT3 receptor antagonists ; Ondansetron ; MDL72222 ; Indirect 5-HT agonist ; Dexfenfluramine ; Opioid reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of the present study was to examine the effects of the 5-HT3 antagonists ondansetron and MDL72222, and the 5-HT releaser and reuptake inhibitor dexfenfluramine, on intravenous heroin self-administration by Wistar rats. Using separate squads of animals, two separate schedules of heroin reinforcement were used; a relatively low dose (0.03 mg/kg per infusion) made available under a FR5 schedule for 1 h each day, and a moderate heroin dose (0.1 mg/kg per infusion) available under a FR1 schedule for 2 h each day. Following the acquisition of stable levels of responding across days, both naloxone pretreatment (0.25 mg/kg SC) and halving the heroin infusion dose produced increases in operant responding for heroin at each concentration. Neither ondansetron (0.01–1 mg/kg SC) nor MDL72222 (0.1–3 mg/kg SC) pretreatment influenced heroin self-administration. Chronic treatment (5 day) of ondansetron (0.01–0.1 mg/kg) was similarly ineffective. However, dexfenfluramine (0.5–2.5 mg/kg IP) consistently reduced heroin self-administration at doses producing only modest decreases in food responding. These findings are in contrast to place conditioning studies, which show that 5-HT3 antagonists but not indirect 5-HT agonists block a morphine-induced place preference. Reasons for such discrepancies remain to be determined.
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  • 119
    ISSN: 1432-2072
    Keywords: (R)-α-Methylhistamine ; Scopolamine ; Histamine ; Cognition ; Water maze ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of (R)-α-methylhistamine ((R)-α-MeHA, a selective H3-receptor agonist) and scopolamine (SCOP, a muscarinic antagonist) were investigated on spatial learning and memory in the rat (Hooded Lister) using a water maze (WM). (R)-α-MeHA treatment (6.3 and 10 mg/kg IP) had no apparent effect on spatial learning but did result in enhanced spatial recall at the higher dose, assessed by a transfer (probe) test after training. In contrast, SCOP (0.5 mg/kg IP) induced a learning and memory deficit measured both during and after training. In animals treated with (R)-α-MeHA and SCOP, (R)-α-MeHA partially (6.3 mg/kg) and completely (10 mg/kg) reversed the SCOP-induced deficit during the training phase, while in the post-training transfer test, (R)-α-MeHA (10 mg/kg) significantly reduced the SCOP-induced memory deficit. None of the treatments described resulted in impaired visual acuity as demonstrated by a raised platform test. These results are consistent with a role for histamine in cognitive processes and suggest a possible interaction between central histamine and cholinergic mechanisms associated with rodent spatial learning and memory.
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  • 120
    ISSN: 1432-2072
    Keywords: Social recognition ; Cognition ; Social interaction ; Ethological method ; Tetrahydroaminoacridine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two major difficulties confront ethopharmacological investigations on cognitive abilities such as social recognition in drug-treated animals involved in free social interactions. The first concerns the choice of the most relevant behaviours, those reflecting the cognitive abilities attributed to the animals and assessing the specificity of the drug activity, and those reflecting non-specific drug effects. The second refers to the experimenter's awareness that in contrast to physical objects, social stimuli respond to drug-treated subjects and that their own level of responsiveness may influence the changes of drug-treated subjects' social interest. In addition, their contribution may vary according to the different treatments the drug-treated subjects receive. In examining the effects of tetrahydroaminoacridine (THA) at doses of 0.3, 1 and 3 mg/kg on the ability of adult male rats to recognize previously encountered conspecifics, we attempted to take into consideration such difficulties. A detailed behavioural profile of drug-treated rats was reported to separate specific from non-specific effects of THA. In addition, rats were assigned an index of responsibility for contact which takes into account the interactive dimension of each dyad and allows relevant comparisons between different treatments. The doses of THA which were found to decrease the duration of exploration of a familiar juvenile were also found to decrease the number of contacts initiated by the drug-treated subjects. THA induced a relative increase in body care by comparison to saline treatment. However, it had no effect of locomotor activity and rearing of the subjects. These findings enable dissociation of the effects of THA on cognitive versus non-cognitive processes.
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  • 121
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 213-220 
    ISSN: 1432-2072
    Keywords: Divided attention ; Scopolamine ; Chlordiazepoxide ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract “Divided attention” is a psychological construct that hinges on assumptions about a fixed finite capacity of subjects to simultaneously process multiple sets of information. A model of a crossmodal divided attention task was developed in rats. Initially, rats were trained consecutively in operant auditory and visual conditional discrimination tasks. The final task consisted of two successive blocks of 20 trials per modality (modality certainty), followed by 60 trials comprising a semi-randomized sequence of stimuli of both modalities (auditory or visual) and qualities (flashing/pulsing or constantly turned on; modality uncertainty). In comparison to unimodal blocks of trials, performance in the mixed condition was assumed to reflect the demands on the parallel processing of two sets of stimulus-response rules. While response accuracy remained unchanged, response latencies were generally longer in the bimodal condition. Administration of scopolamine (0.03, 0.06, 0.1 mg/kg) or chlordiazepoxide (1, 3, 5, 8 mg/kg) dose-dependently increased response latencies. The scopolamine-induced increase in response latencies was greater in the mixed condition. Cost-benefit analyses demonstrated that the absolute divided attention costs (in ms) were generally higher for visual than for auditory stimuli. Both drugs produced qualitatively similar effects; however, scopolamine was more potent in increasing the absolute divided attention costs than chlordiazepoxide. These data are discussed in terms of the validity of this animal paradigm, and of hypotheses about the effects of benzodiazepine receptor agonists and muscarinic antagonists on brain information processing capacity.
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  • 122
    ISSN: 1432-2072
    Keywords: Behaviour ; Olfactory recognition ; Social investigation ; Neuropeptides ; Cholecystokinin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Modulation of learning and memory is one of the physiological roles that the neuropeptide cholecystokinin (CCK-8) may play. We have used a behavioural model of olfactory recognition among rats to test this hypothesis and to explore the relationship between CCK-A and CCK-B receptors and memory retention. Adult male rats form a transient memory of a juvenile congenere as indicated by a reduction in the duration of investigatory behaviour upon re-exposure 30 min after an initial exposure, but not when re-exposure is delayed until 120 min afterwards. In the present study, rats were treated after the first contact with various compounds; inhibition and facilitation of olfactory recognition were evaluated as the persistence in investigation 30 min and the decrease in investigation 120 min after pharmacological manipulations, respectively. Systemic injection of CCK-8, of a selective CCK-A agonist, or of non-peptide CCK-B antagonists (CI-988 and LY-262691) enhanced olfactory recognition. In contrast, the CCK-B selective agonist BC 264 and the tetrapeptide CCK-4 both disrupted it. Taken together with previous evidence of the detrimental effect of the non-peptide CCK-A antagonist devazepide on olfactory recognition, these results confirm and extend the hypothesis that there is a balance between CCK-A-mediated facilitative effects and CCK-B-mediated inhibitory effects on memory retention.
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  • 123
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Imipramine ; Animal model of depression ; Dopamine ; D1-receptors ; D2-receptors ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild stressors has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, associated with abnormalities of dopaminergic neurotransmission in the nucleus accumbens. In the present study, 5 weeks of treatment with imipramine (10 mg/kg b.i.d.) reversed the decreased sucrose intake of rats exposed to chronic mild stress. Stress also caused a decrease in D2-receptor binding in the limbic forebrain (but not the striatum), which was completely reversed by imipramine. In nonstressed animals, imipramine decreased D1-receptor binding in both regions. However, in stressed animals, imipramine did not significantly alter D1-receptor binding in either area. Stress alone slightly increased D1-receptor binding, in striatum only. Scatchard analysis showed that all changes in receptor binding resulted from changes in receptor number (Bmax) rather than receptor affinity (KD). The results support the hypothesis that changes in D2-receptor function in the nucleus accumbens are responsible for chronic mild stress-induced anhedonia and its reversal by antidepressant drugs. They do not support the hypothesis that the sensitization of D2-receptors seen following chronic antidepressant treatment is caused by a down-regulation of D1-receptors.
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  • 124
    ISSN: 1432-2072
    Keywords: β1-adrenergic receptors ; Rat ; Brain ; Citalopram ; Fluoxetine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of β1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg−1), fluoxetine (10 mg kg−1), or imipramine (15 mg kg−1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to β1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in β1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg−1) or fluoxetine (2.5, 10 and 20 mg kg−1) SC once daily for 14 days. The effects of citalopram and fluoxetine on β1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of β1-adrenergic receptors in the rat brain.
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  • 125
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Interval bisection procedure ; Acquisition ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition and performance of discrimination between two brief time intervals. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats were trained in a series of discrete trials to press lever A following a 200-ms presentation of a light stimulus and lever B following an 800-ms presentation of the same stimulus. Both groups gradually acquired accurate performance, attaining 80%–85% accuracy by the end of 40 sessions. The lesioned group learnt the task significantly faster than the control group. When stable performance had been attained, “probe” trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. The bisection point (duration corresponding to 50% choice of lever B) did not differ significantly between the two groups; however, the Weber fraction was significantly smaller in the lesioned group than in the control group. The levels of 5HT and 5-hydroxy-indole-acetic acid were markedly reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. The results indicate that destruction of the 5HTergic pathways facilitates acquisition of a temporal discrimination. The lack of an effect of the lesion on the bisection point contrasts with our previous finding using longer stimulus durations; it is suggested that different behavioural processes may underlie millisecond-range and second-range temporal discrimination, and that these may be differently affected by 5HT depletion.
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  • 126
    ISSN: 1432-2072
    Keywords: Antipsychotic agents ; Acoustic startle ; Prepulse inhibition ; Schizophrenia ; Phencyclidine ; Remoxipride ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of various typical (haloperidol) and atypical (clozapine, raclopride, remoxipride) antipsychotics on phencyclidine (PCP)-induced disruption of sensorimotor gating was tested in rats using an acoustic startle paradigm. Clozapine (4–40 µmol/kg), haloperidol (1–5 µmol/kg) and raclopride (1–12 µmol/kg) failed to reverse PCP-induced disruption of prepulse inhibition (PPI) of the acoustic startle response. In contrast, remoxipride (12–60 µmol/kg) caused a dose-dependent block of this effect. PCP-induced disruption of PPI is a widely accepted animal model of a corresponding behavioural deficit observed in schizophrenia although little evidence has been presented that it is in fact sensitive to antipsychotic agents. The present results indicate that remoxipride behaves in a unique way in this model compared to clozapine, haloperidol and raclopride.
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  • 127
    ISSN: 1432-2072
    Keywords: Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.
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  • 128
    ISSN: 1432-2072
    Keywords: Neurosteroid ; Memory ; Amnesia ; NMDA receptor ; Ataxia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The neurosteroid pregnenolone sulfate (PS) has been recently shown to positively modulate NMDA receptors and to have memory enhancing properties in mice. In the present study, we examined the ability of PS to increase retention performance and to reduce deficits induced by a competitive NMDA receptor antagonist, the 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), in a step-through passive avoidance task in rats. Pretraining administration of PS (0.84–1680 pmol, ICV) had minimal effects on retention performance assessed 24 h after training, while CPP significantly decreased retention performance at the doses of 1.2 and 1.6 nmol (ICV). However, when administered in combination with CPP (1.2 nmol), PS (0.84–840 pmol, ICV) dose-dependently blocked the deficit in passive avoidance response induced by the NMDA antagonist. At the dose of 840 nmol, PS also significantly reduced the motor impairment induced by CPP (1.2 nmol). The blockade of CPP-induced behavioral deficits by PS may result from its positive modulatory action at NMDA receptors.
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  • 129
    ISSN: 1432-2072
    Keywords: Fetus ; Prenatal drug exposure ; Schizophreniad-Amphetamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent evidence suggests that mid-pregnancy is a critical period for production of fetal abnormalities that cause behavioral and neuropathological changes in adult offspring. The present experiments provide an animal model of these effects by treating pregnant Sprague-Dawley rats during gestational days 11–14 withd-amphetamine (AM). Offspring were tested for neurological signs, foraging activity, reversal learning, and sensitivity to amphetamine challenge. In the Early Juvenile period, postnatal days (PND) 20–30, female AM offspring initially showed reductions in rearing, holepoking, and midfield activity. On later trials, and as young adults, AM females showed signs of locomotor hyperactivity despite continued poor foraging efficiency, and were also more sensitive to a 1.0 mg/kgd-amphetamine challenge. AM males showed initially slower and more perseverative responding than controls, but then developed excessive response switching. These changes continued during tests for Retention, Reversal, and Extinction in the Late Juvenile/Early Adult stage (PND 50–90), when both AM-exposed sexes showed increased eating time, significantly more perseverative lateral turning preference (right or left), and slower reversal learning than controls. Behavioral data were consistent with aberrations in thalamo-frontal and mesolimbic/nigrostriatal projection systems that have been reported in AM animals and which are also affected by maternal drug abuse and schizophrenia.
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  • 130
    ISSN: 1432-2072
    Keywords: Adenosine A2 receptor ; Dopamine D2 receptor ; Methylxanthine ; Tardive dyskinesias ; Receptor-receptor interaction ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Stimulation of adenosine A2 receptors (with the selective adenosine A2 agonist CGS 21680) in rat striatal membrane preparations, produces a decrease in both the affinity of D2 receptors and the transduction of the signal from the D2 receptor to the G protein. This intramembrane A2-D2 interaction might be responsible for the behavioural depressant effects of adenosine agonists and for the behavioural stimulant effects of adenosine antagonists such as caffeine and theophylline. Dopamine denervation induces an increase in the intramembrane A2-D2 interaction, which may underlie the observed higher sensitivity to the behavioural effects induced by adenosine antagonists found in these animals. The present study was designed to examine if chronic treatment with haloperidol, which also produces dopamine receptor supersensitivity, is also associated with an increase in the intramembrane A2-D2 interaction in the neostriatum and with a higher sensitivity to the behavioural effects induced by adenosine antagonists. The data showed that: (i) haloperidol pretreatment causes a higher binding of the D2 antagonist [3H] raclopride in striatal membrane preparations due to an increase in the number of D2 receptors without changes in their affinity for the antagonist (increase in Bmax without changes in kd); (ii) GCS 21680 decreases the affinity of dopamine for the D2 receptor, by increasing the equilibrium dissociation constants of high (Kh) and low affinity (K1) dopamine D2 binding sites and increases the proportion of high affinity binding sites (Rh); (iii) a low dose of CGS 21680 (3 nM), which is ineffective in membrane preparations from neostriatum of nontreated animals, is effective in membranes from the striatum of haloperidol-pretreated animals; (iv) the nonselective adenosine antagonist theophylline (20 mg/kg SC) causes a higher motor activation in rats pretreated with haloperidol. The possible relevance of these results for the pathophysiology and treatment of tardive dyskinesias is discussed.
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  • 131
    ISSN: 1432-2072
    Keywords: Rat ; Development ; Δ-9-Tetrahydrocannabinol ; Motor behavior ; Locomotor activity ; Grooming ; Corticosterone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to Δ9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone. These results confirm our previous finding of a sex-dimorphic behavioral response to perinatal exposure to hashish extracts, and they suggest a role of THC-induced PA activation in the mediation of these actions.
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  • 132
    ISSN: 1432-2072
    Keywords: Dopamine ; 5-HT2 ; 5-HT1C ; D1 ; SKF 38393 ; SKF 82958 ; SCH 39166 ; SCH 23390 ; Feeding ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hypophagic effect of the D1 receptor agonist SKF 38393 is not dose-dependently antagonized by the D1 antagonist SCH 23390. Moreover, the receptor specificity of this interaction remains in question, since SCH 23390 has significant activity at both 5-HT2 and 5-HT1C receptors, and SKF 38393 also interacts with 5-HT1C receptors. To determine the relative significance of these actions, a comparison was made between the anorectic effects in rats of SCH 23390 (0.1–1.0 mg/kg) and the benzonaphthazepine SCH 39166 (0.1–3.0 mg/kg), a D1 antagonist with negligible affinity for 5-HT sites. Both compounds inhibited food-intake dose-dependently, with SCH 23390 being approximately twice as potent as SCH 39166. Behaviorally inactive and active doses of both antagonists were tested in combination with the D1 agonist SKF 38393 (10–56 mg/kg). Neither antagonist was able to produce more than a marginal attenuation of the agonist-induced hypophagia. This demonstrates that previous failures to reverse the behavioral actions of SKF 38393 by SCH 23390 were not due to specific actions of this particular antagonist. Finally, like SCH 23390, SCH 39166 (0.3 mg/kg) was able to attenuate fully the anorectic effects of the D1 agonist SKF 82958 (1.0 and 3.0 mg/kg), demonstrating that neither compound is intrinsically unable to block D1 receptor-mediated hypophagia. The results demonstrate the generality of the D1 antagonist-mediated effect on feeding and call into question the use of SKF 38393 as a D1 agonist in studies of feeding, and perhaps in other contexts as well.
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  • 133
    ISSN: 1432-2072
    Keywords: Prefrontal cortex ; Dopamine ; Acoustic startle response ; Prepulse inhibition ; 6-Hydroxydopamine ; Rat ; Schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prepulse inhibition (PPI) of the acoustic startle response (ASR) is impaired by dopamine (DA) overactivity in the nucleus accumbens and anteromedial striatum. Since there is evidence that DA in the medial prefrontal cortex exerts an inhibitory control on striatal DA systems, it was investigated whether depletion of prefrontal DA reduces PPI. Rats were tested for PPI both before and after injections (2 × 1 µl per side) of vehicle, a low (3.0 µg/µl) or a high (6.0 µg/µl) dose of 6-hydroxydopamine hydrobromide (6-OHDA) into the prefrontal cortex. Only the high dose of 6-OHDA, leading to an 87% depletion of prefrontal DA, impaired PPI. The ability of an acoustic prepulse (75 dB, 10 kHz) to reduce the response to a startle pulse (100 dB noise burst) was maintained in sham lesioned rats, but was significantly disturbed in rats lesioned with the high dose of 6-OHDA. The 6-OHDA treatment did not affect the ASR amplitude in the absence of a prepulse. The reduction of PPI in lesioned rats correlated with the extent of DA depletion. These results suggest that the DA innervation of the prefrontal cortex is involved in the modulation of the ASR and they provide further evidence for opposite actions of prefrontal and subcortical DA systems in the control of behaviour. The present findings are discussed with regard to the potential role of prefrontal DA in schizophrenia.
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  • 134
    ISSN: 1432-2072
    Keywords: Risperidone ; 9-Hydroxy-risperidone ; Active metabolite ; Antipsychotic ; 5-HT2 Antagonist ; Dopamine-D2 antagonist ; Pharmacokinetics ; Regional brain distribution ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Risperidone is a new benzisoxazole antipsychotic. 9-Hydroxy-risperidone is the major plasma metabolite of risperidone. The pharmacological properties of 9-hydroxy-risperidone were studied and appeared to be comparable to those of risperidone itself, both in respect of the profile of interactions with various neurotransmitters and its potency, activity, and onset and duration of action. The absorption, plasma levels and regional brain distribution of risperidone, metabolically formed 9-hydroxy-risperidone and total radioactivity were studied in the male Wistar rat after single subcutaneous administration of radiolabelled risperidone at 0.02 mg/kg. Concentrations were determined by HPLC separation, and off-line determination of the radioactivity with liquid scintillation counting. Risperidone was well absorbed. Maximum plasma concentrations were reached at 0.5–1 h after subcutaneous administration. Plasma concentrations of 9-hydroxy-risperidone were higher than those of risperidone from 2 h after dosing. In plasma, the apparent elimination half-life of risperidone was 1.0 h, and mean residence times were 1.5 h for risperidone and 2.5 h for its 9-hydroxy metabolite. Plasma levels of the radioactivity increased dose proportionally between 0.02 and 1.3 mg/kg. Risperidone was rapidly distributed to brain tissues. The elimination of the radioactivity from the frontal cortex and striatum—brain regions with high concentrations of 5-HT2 or dopamine-D2 receptors—became more gradual with decreasing dose levels. After a subcutaneous dose of 0.02 mg/kg, the ED50 for central 5-HT2 antagonism in male rats, half-lives in frontal cortex and striatum were 3–4 h for risperidone, whereas mean residence times were 4–6 h for risperidone and about 12 h for 9-hydroxy-risperidone. These half-lives and mean residence times were 3–5 times longer than in plasma and in cerebellum, a region with very low concentrations of 5-HT2 and D2 receptors. Frontal cortex and striatum to plasma concentration ratios increased during the experiment. The distribution of 9-hydroxy-risperidone to the different brain regions, including frontal cortex and striatum, was more limited than that of risperidone itself. This indicated that 9-hydroxy-risperidone contributes to the in vivo activity of risperidone, but to a smaller extent than would be predicted from plasma levels. AUCs of both active compounds in frontal cortex and striatum were 10–18 times higher than those in cerebellum. No retention of metabolites other than 9-hydroxy-risperidone was observed in any of the brain regions investigated.
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  • 135
    ISSN: 1432-2072
    Keywords: Cocaine ; Drug discrimination ; Nucleus accumbens ; Dopamine D1 and D2 receptors ; Microinjection ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accum bens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625–20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5–40 µg) into the nucleus accumbens also engendered dose-dependent and complete substitutions (〉 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 µl/side) produced primarily saline-appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3–12 µg/kg) completely antagonized (〈20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025–0.4 µg) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior.
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  • 136
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 115 (1994), S. 289-296 
    ISSN: 1432-2072
    Keywords: CL 284,846 ; Drug discrimination ; Sedative ; Hypnotic ; Anxiolytic ; Rat ; Benzodiazepine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CL 284,846,N-[3-(3-cyanopyrazolo[1, 5-a]pyrimidin-7-yl)phenyl)]-N-ethylacetamide, is a novel non-benzodiazepine sedative-hypnotic with benzodiazepine-like sedative effects, but with less apparent liability for accompanying undesired side effects. In an effort to further characterize its pharmacological activity, CL 284,846 (3.0 mg/kg, IP, 30 min pretreatment) was established as a discriminative stimulus (DS) in rats (n=7). CL 284,846 (0.3–10.0 mg/kg) showed a dose-related increase in drug-appropriate responding up to the training dose and a dose-related decrease in response rate. The benzodiazepine agonist triazolam (0.1–1.0 mg/kg), the benzodiazepine partial agonist Ro 17-1812 (0.3–3.0 mg/kg) and the triazolopyridazine CL 218,872 (1.0–3.0 mg/kg) substituted for CL 284,846 in all rats, whereas the imidazopyridines zolpidem (3.0–10.0 mg/kg) and alpidem (10.0–30.0 mg/kg), the benzodiazepine partial agonist bretazenil (0.03–10.0 mg/kg) and the novel putative anxiolytic CL 273,547 (10.0–56.0 mg/kg) substituted in most, but not all, rats. Ro 17-1812, bretazenil, and CL 218,872 had no effect on response rate while the other drugs showed a concomitant decrease in rate. The 5-HT1A agonist buspirone (1.0–10.0 mg/kg) and the barbiturate pentobarbital (3.0–17.0 mg/kg) failed to substitute for CL 284,846 up to rate-decreasing doses. The benzodiazepine antagonist flumazenil (3.0–10.0 mg/kg) blocked the DS effects of CL 284,846 in most rats with no effect on response rate. Taken together, these results suggest that the DS effects of CL 284,846 are mediated via benzodiazepine receptors; however, the DS profile of CL 284,846 remains distinct from both benzodiazepine and non-benzodiazepine sedative-hypnotic drugs.
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  • 137
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    Psychopharmacology 115 (1994), S. 320-324 
    ISSN: 1432-2072
    Keywords: Caffeine ; Electroconvulsive shock ; Seizure ; Rat ; Electroencephalography ; Convulsions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Caffeine has been used clinically to increase seizure length in electroconvulsive treatment (ECT). The present study was designed to establish an animal model of caffeine-augmented seizures for further study of mechanisms and effects of pharmacological manipulation of seizure length. Increasing doses of caffeine (0–200 mg/kg, IP) were given before electroconvulsive stimulation (ECS) in rats and resulting seizure lengths were quantified by timing of classical tonic-clonic convulsive movements. With this paradigm, caffeine led to a dose-dependent increase in seizure duration. This proconvulsant action of caffeine was detectable within 1 min after dosing, persisted for at least 230 min and was reversible. The results suggest that seizure length is a practicable measure in pharmacological modification of electroconvulsive seizures. They also suggest that pharmacologically-modified ECS can be modeled effectively in animals.
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  • 138
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    Psychopharmacology 115 (1994), S. 249-253 
    ISSN: 1432-2072
    Keywords: Penile erection ; Muscimol ; Baclofen ; Bicuculline ; Picrotoxin ; Phaclofen ; Apomorphine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01–0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1–0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).
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  • 139
    ISSN: 1432-2072
    Keywords: Dopamine receptors ; Neuroleptics ; SCH-23390 ; Raclopride ; Response duration ; Catalepsy ; Operant behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an experiment designed to distinguish between the behavioral consequences of treatment with SCH-23390, a D1 dopamine receptor blocker, and raclopride, a D2 antagonist, rats were trained to perform a water-reinforced forelimb operant response. Response rate and the duration of each forelimb contact with the operandum were recorded. In addition, the durations of the rat's visits to the reward well were detected by a photobeam which was blocked by the rat's muzzle as it remained at the reward well. In a between-groups dosing design, separate groups of rats (11–13 rats/group) received SCH-23390 (0, 0.01, 0.02, 0.04, 0.08, 0.12 mg/kg, IP, 30 min) or raclopride (0. 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg, IP, 30 min) for 21 consecutive days. Quantitative analyses indicated that for comparable amounts of operant rate reduction, raclopride had a significantly greater tendency than SCH-23390 to increase the duration of operant responses and to increase the maximum muzzle entry duration (i.e., to induce microcatalepsy). The results support the idea that at relatively low doses D2 antagonism is more likely than D1 antagonism to produce effects identified preclinically with extrapyramidal side effects.
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  • 140
    ISSN: 1432-2072
    Keywords: Cocaine ; Schedule-induced polydipsia ; Drinking ; Locomotor activity ; Nucleus accumbens ; Medial prefrontal cortex ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cocaine HCl infusions into either the nucleus accumbens (NACC) or medial prefrontal cortex (PFC) were compared on the performance of schedule-induced polydipsia (SIP) and related behaviours. Food-deprived rats were exposed to a fixed-time 60-s schedule of food delivery in daily 30-min sessions until stable levels of behaviour were obtained (14 days). Rats were then bilaterally infused with cocaine into either the NACC or PFC via chronically indwelling guide cannulae. Each subject received a sequence of five cocaine infusions (0, 12.5, 25, 50, 100 µg) according to a Latin Square design. For comparison, following these intracranial infusions each rat received a sequence of five IP injections of cocaine (0, 2.5, 5, 10, 20 mg/kg) also in a counterbalanced order. NACC and PFC infusions of cocaine and IP cocaine dose-dependently reduced SIP. Cocaine infusions into the NACC, but not the PFC, increased locomotor activity but the characteristic temporal profile of locomotor activity during SIP was retained. IP cocaine also increased locomotor activity in a dose-dependent manner, but the temporal profile of activity was flattened following 20 mg/kg cocaine. NACC and PFC infusions of cocaine had little effect on the total number of panel presses to gain access to the food pellets, but did slightly decrease the high rates of responding immediately prior to the pellet delivery. IP cocaine increased the total number of panel presses at the higher doses, mainly by increasing the low rates of responding. The effects of cocaine infusions into the PFC were behaviourally the most selective, as they reduced SIP without having substantial effects either on locomotor activity or panel pressing. These data therefore implicate a role for the PFC in the performance of SIP.
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  • 141
    ISSN: 1432-2072
    Keywords: Anxiety ; Elevated zero-maze ; Rat ; Diazepam ; Chlordiazepoxide ; mCPP ; 8-OH-DPAT ; Ondansetron ; Head dips ; Stretched attend postures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The elevated “zero-maze” is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125–0.5 mg/kg) and chlordiazepoxide (0.5–2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drugm-chlorophenyl-piperazine (mCPP; 0.25–1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001–0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001–1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel “zero-maze” design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.
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  • 142
    ISSN: 1432-2072
    Keywords: 5-HT1B ; 5-HT1C ; 5-HT2 receptors ; Feeding ; Satiety sequence ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have shown that administration of 5-HT1B, 5-HT1C or 5-HT2 agonists decreases food intake in rats. However, it has not been established whether these drugs induce satiety or decrease feeding by a non-specific mechanism. In the present study the post-prandial satiety sequence was used to characterise the actions of the 5-HT2 receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5-HT1B/5-HT1C receptor agonists, 1-(3-chorophenyl) piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), and the 5-HT1B agonist, 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)H-indole (RU 24969), on feeding in rats. All four compounds reduced food intake in rats that had been food deprived overnight. The 5-HT1B/5-HT1C agonists, TFMPP (at a dose of 1.0 mg/kg) and mCPP (at a dose of 3.0 mg/kg), appeared to produce satiety as their effects on the satiety sequence were similar to those induced by a food pre-load. In contrast, the 5-HT1B agonist RU 24969 and the 5-HT2 agonist DOI did not produce behavioural profiles that resembled satiety. Thus, RU 24969 elevated active behaviours and did not accelerate resting whereas DOI appeared to induce hypophagia by a non-specific fragmentation of behaviour. The results suggest that simultaneous activation of 5-HT1B and 5-HT1C receptors may be sufficient to elicit behaviourally specific satiety in the rat. In contrast, selective activation of 5-HT2 receptors does not induce satiety but elicits active behaviours and decreases feeding by response competition.
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  • 143
    ISSN: 1432-2072
    Keywords: Behavioral sensitization ; amphetamine ; NPA ; Ontogeny ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, the abilities of NPA (a direct DA receptor agonist) and amphetamine (an indirect DA receptor agonist) to induce short- and long-term behavioral sensitization were assessed in 11- and 17-day-old rats (age at initial injection). Rats were injected on 4 consecutive days with amphetamine (1.0, 2.5, or 5.0 mg/kg), NPA (1.0 mg/kg), or saline. A final test day occurred either 2 days (experiment 1) or 8 days (experiment 2) later. On the test day, rats given successive agonist injections received a single injection of the same agonist again; whereas rats given successive saline injections received either amphetamine or NPA for the first time. Five minutes after injection, locomotor activity (line-crosses), stereotyped sniffing, and vertical activity were measured during a 30-min testing session. The results showed that 11- and 17-day-old rats exhibited behavioral sensitization when tested with NPA or amphetamine after a 2-day interval. In contrast, neither NPA nor amphetamine was able to sensitize the behaviors of preweanling rats when measured 8 days after initial drug treatments. Therefore, these results show that both direct and indirect DA agonists are able to induce short-term behavioral sensitization in preweanling rats, but that the mechanisms responsible for mediating long-term behavioral sensitization have not yet matured.
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  • 144
    ISSN: 1432-2072
    Keywords: Stress ; Anxiety ; Rat ; Metabolism ; Energy expenditure ; Energy substrate utilisation ; Respiratory quotient ; Midazolam ; FG-7142 ; RO 15-1788 ; Panic ; Hyperventilation ; Sympathetic nervous system ; Benzodiazepine ; Conditioned stimulus ; Respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Changes in O2 consumption, CO2 production and locomotor activity were examined in rats exposed to (1) brief footshock, (2) an aversive conditioned stimulus (CS) predicting footshock, or (3) the anxiogenic drug FG-7142. Respiratory quotient (RQ=CO2 produced/O2 consumed) and energy expenditure [EE=O2 consumed (364+113RQ)] were derived to give an estimate of the energy substrate (fat, carbohydrate or protein) being utilised and total substrate oxidation respectively. In experiment 1, footshock (4 × 5 s 0.6 mA shocks over 2 min) produced an immediate increase in RQ, EE and activity. The RQ and EE effects were attenuated by the benzodiazepine midazolam (1 mg/kg). In experiment 2, an aversive CS, consisting of flashing light and buzzer that had 24 h earlier been repeatedly paired with footshock (20 × 5 s 0.6 mA shocks) caused a pronounced drop in RQ, an increase in EE and locomotor activity suppression. The effects of the aversive CS on RQ and EE were reversed by midazolam (1 mg/kg). In experiment 3, FG-7142 (10 mg/kg) produced a steep drop in RQ that persisted for at least 2 h and which was reversed by midazolam (1 mg/kg) and delayed by the benzodiazepine antagonist RO 15-1788 (10 mg/kg). FG-7142 also tended to inhibit EE and locomotor activity, but these effects did not reach statistical significance. Overall, these data show that stress causes profound alterations in RQ, EE and activity and that the pattern of change in these parameters differs with the nature of the stressor involved.
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  • 145
    ISSN: 1432-2072
    Keywords: Kavapyrone ; Piper methysticum ; GABA ; Rat ; Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plantPiper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 µM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 µM the order of enhancement in Bmax was HIP=AMY〉MED〉FC〉CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.
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  • 146
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    Psychopharmacology 113 (1994), S. 534-538 
    ISSN: 1432-2072
    Keywords: Nicotine ; Prenatal ; Analgesia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.
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  • 147
    ISSN: 1432-2072
    Keywords: 5-Hydroxytryptamine ; 5,7-Dihydroxytryptamine ; Operant behaviour ; Timing ; Fixed-interval peak procedure ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twelve rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei; 12 rats received sham lesions. The rats were then trained for 60 sessions under a discrete-trials fixed-interval schedule (peak procedure). In half the trials, a reinforcer became available 40 s after trial onset, and the trial was terminated upon reinforcer delivery; the remaining trials were 120 s in duration, and reinforcement did not occur in these trials. Performance during the 120-s trials was characterized by increasing response rate during the first 40 s of the trial, declining response rate between 40 s and 80 s, and a secondary increase in response rate during the final 40 s of the trial. The lesioned group showed a broader “spread” of the response rate function than the control group (time between attainment of 70% of the peak response rate and subsequent decline of response rate below this level); however, the peak response rate and the time from trial onset until attainment of the peak response rate did not differ significantly between the groups; the spread/peak-time ratio was significantly greater in the lesioned group than in the control group. The levels of 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acid in the parietal cortex, hippocampus, amygdala, nucleus accumbens and hypothalamus were markedly reduced in the lesioned group, but the levels of noradrenaline and dopamine were not significantly affected by the lesion. The results confirm the involvement of 5HTergic function in timing behaviour.
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  • 148
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal ; Acoustic startle ; Spatial learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-MA (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions.
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  • 149
    ISSN: 1432-2072
    Keywords: Phenylpropanolamine ; Body weight ; Food consumption ; Water consumption ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study determined the effect of chronic PPA infusion and withdrawal on weight regulation. Male Sprague-Dawley rats received PPA (0, 90 or 180 mg/kg) via miniosmotic pumps for 2 weeks. Body weight and food and water consumption were measured daily before, during, and for 2 weeks after PPA infusion. Additionally, body weight was measured once 6 weeks after the last day of drug administration. PPA infusion produced dose-dependent reductions in body weight and food consumption throughout drug administration. During the first week of PPA termination, food consumption returned to control levels; however, body weights of drug-treated animals remained below those of controls throughout the 6-week post-drug period. PPA depressed water intake during the first week of drug administration, but tolerance to this effect developed by the second week of administration. These results suggest chronic PPA infusion produces persistent appetite suppression and weight loss and that discontinuation of PPA does not result in hyperphagia or rapid weight gain. These findings may have clinical significance for the many individuals who wish to lose weight but have difficulty reducing intake without pharmacologic assistance.
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  • 150
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; Diazepam ; Morris water maze ; Place learning ; Anxiety ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anxiolytic benzodiazepines have been shown to impair place learning in the Morris water maze. However, a clear-cut demonstration of a direct and specific effect on mnemonic processes has not yet been offered. In the present study, the effects of diazepam on place navigation in the Morris water maze were studied in rats. Three conditions were examined: learning, reversal learning and learning after familiarisation of animals with the maze. In view of the anxiolytic and sedative properties of diazepam, appropriate doses of the drug, i.e. those that produced an anxiolytic effect but no major motor impairment, were initially selected in the water-lick conflict and rotarod tests, respectively. Doses of 2.5 and 5 mg/kg PO increased punished drinking in the water-lick conflict test without significantly decreasing rotarod performance. These doses were then used to assess the effects of diazepam on spatial behaviour. Diazepam, at both doses, impaired place learning in behaviourally naive rats. Such an effect appeared to be transient: diazepam-treated rats eventually reached control performance. Moreover, analysis of the probe trial at the end of training revealed adoption of a spatial strategy to locate the submerged platform. Neither reversal learning nor learning after familiarisation was affected. These results do not replicate previous findings in the Morris water maze and provide some evidence that the diazepam-induced place learning deficit may be primarily anxiolytic in nature.
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  • 151
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    Psychopharmacology 115 (1994), S. 478-484 
    ISSN: 1432-2072
    Keywords: Aggression ; α2 Adrenoceptors ; Catecholamines ; ACTH ; Corticosterone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α2 adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α2 adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α2 adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α2 adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.
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  • 152
    ISSN: 1432-2072
    Keywords: Isolation rearing ; α2-Adrenoceptor ; Clonidine ; Mydriasis ; Hypoactivity ; [3H]-Idazoxan binding ; cAMP ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated central α2-adrenoceptor function in differentially reared rats. Rats reared from weaning were either housed singly or in groups of five. Measurements of spontaneous ambulatory activity at 4 weeks postweaning showed that isolates were more hyperactive on exposure to a novel environment than grouped rats. α2-Adrenoceptors were investigated using α2-adrenoceptor agonist-induced behaviours, [3H]-idazoxan binding and measurement of forskolin-stimulated cyclic AMP accumulation. Clonidine (0.001–1.0 mg/kg IP) induced mydriasis in both groups with no difference observed in the response between the isolation and group-reared animals. Clonidine (0.01–0.5 mg/kg IP) induced hypoactivity in both groups, with the effect significantly greater in the isolation-reared rats. Idazoxan markedly attenuated both responses, confirming their induction by α2-adrenoceptor stimulation. Clonidine-induced hypoactivity and mydriasis are mediated by pre- and postsynaptic α2-adrenoceptors, respectively; therefore the results suggest rats reared in isolation have enhanced presynaptic but unchanged postsynaptic α2-adrenoceptor function. Saturation binding experiments using [3H]-idazoxan were undertaken to determine α2-adrenoceptor number (Bmax) and affinity (Kd) in membranes prepared from the frontal cortex and hippocampus. Analysis of binding data revealed an increase in receptor number in the hippocampus of isolates. Cyclic AMP accumulation was measured in hippocampal slices from differentially reared rats. Isolation-rearing did not affect cyclic AMP accumulation in response to stimulation by forskolin (30 µM). However, the selective α2-adrenoceptor agonist, UK14304, produced a significantly greater inhibition of cyclic AMP accumulation in slices from isolated rats, confirming changes in α2-adrenoceptor function following isolation rearing.
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  • 153
    ISSN: 1432-2072
    Keywords: SR 48692 ; Neurotensin receptor antagonist ; Dopamine ; Apomorphine ; Bromocriptine ; (+) SKF 38393 ; (+) Amphetamine ; Turning ; Yawning ; Mouse ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 – 0.64 mg/kg orally), antagonizes (50–65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 µg), (+) SKF 38393 (0.1 µg), bromocriptine (0.01 ng) or (+) amphetamine (10 µg) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
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  • 154
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    Psychopharmacology 116 (1994), S. 304-308 
    ISSN: 1432-2072
    Keywords: Intermediate stage of sleep ; Paradoxical sleep ; Spindle ; Theta rhythm ; Atropine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Paradoxical sleep (PS) in the rat, cat and mouse is preceded and sometimes followed by a short-lasting intermediate stage (IS) characterized by high amplitude cortical spindles and low frequency theta rhythm. This stage, which is mimicked by an intercollicular transection, is massively extended at the expense of PS by low doses of barbiturates. Since the pontine cholinergic cell activation of PS is suppressed by barbiturates, we studied whether atropine, an antimuscarinic compound, extends IS at the expense of PS. Atropine sulfate was given at 5, 10 and 20 mg/kg IP. All doses increased dose dependently the occurrence latency of IS and PS. The amount of IS and PS was decreased for several hours, principally by a decrease of the number of phases. At 20 mg/kg the phase mean duration of IS and PS was also decreased. Consequently, IS and PS are similarly supported by muscarinic processes. The theta rhythm frequency was scored during IS and outside PS phasic motor activities (type 2 theta). At all doses it was significantly increased for hours. The theta rhythm frequency was also transiently increased during the hypersynchronization periods of PS (type 1 theta). At 20 mg/kg it was similarly the case for type 1 theta rhythm during waking.
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  • 155
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    Psychopharmacology 116 (1994), S. 523-528 
    ISSN: 1432-2072
    Keywords: Chronic mild stress ; Anhedonia ; Sucrose drinking ; Place conditioning ; Mianserin ; (+)-Mianserin ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chronic sequential exposure to a variety of mild unpredictable stressors has previously been found to depress the consumption of a dilute (1%) sucrose solution and to inhibit food-induced place preference conditioning. In the present study, using a simplified version of the mild stress procedure, the decreased sucrose intake was reversed by chronic (4 weeks) treatment with the atypical antidepressant mianserin. The racemic compound (±)-mianserin (5 mg/kg per day) and one of its enantiomers, (+)-mianserin (2.5 mg/kg) were effective in this model; a lower dose of (±)-mianserin (2.5 mg/kg), and the other enantiomer, (−)-mianserin (2.5 mg/kg), were ineffective. Vehicle-treated stressed animals were also subsensitive to food reward in the place conditioning procedure: normal place preference conditioning was reinstated by chronic treatment with (±)-mianserin (5 mg/kg) or (+)-mianserin, but not by the lower dose of (±)-mianserin (2.5 mg/kg) or by (−)-mianserin. Raclopride (100 µg/kg) reinstated the decrease in sucrose intake in stressed animals successfully treated with (±)- or (+)-mianserin. The results suggest that (+)-mianserin is the active enantiomer in reversing chronic mild stress-induced anhedonia, and further support the hypothesis of a dopaminergic mechanism of antidepressant action in this paradigm.
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  • 156
    ISSN: 1432-2072
    Keywords: Methamphetamine ; Rat ; Postnatal development ; Hypoactivity ; Pharmacological challenge
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Methamphetamine induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received little attention. In this experiment the effects of methamphetamine exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously withd-methamphetamine (d-MA) (30 mg/kg b.i.d.) early in postnatal development (days 1–10), later (postnatal days 11–20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited reduced locomotor activity. The effect was most evident at 30 days of age and was smaller at 45 and 60 days and only present at these latter ages in males. Only the early MA exposure group showed prolonged suppression of activity in response to a challenge dose of fluoxetine and a persistant deficit in weight while only the later MA exposure group showed attenuated suppression of activity in response to a challenge dose of fluoxetine. Based both on the present data and those in the preceding article, it was concluded that the effects of MA are both long lasting and stage dependent and involve arousal as well as cognitive functions.
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  • 157
    ISSN: 1432-2072
    Keywords: Cocaine ; Self-administration ; Calcium antagonists ; Isradipine ; Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of isradipine, a dihydropyridine calcium antagonist, on cocaine intravenous self-administration in rats was investigated. Administration of (±)isradipine (1.25–5 mg/kg SC) 2 h before the cocaine self-administration session induced a significant and dose-dependent increase in the number of coacine injections with respect to basal values. This effect was sterospecific, with the (+) form of isradipine being active, while the (−) stereoisomer was ineffective. These results suggest that isradipine antagonizes the rewarding properties of cocaine, possibly by inhibiting those dopaminergic systems related to reward mechanisms. These results further indicate a possible use of isradipine, or structurally similar compounds, in the treatment of cocaine related disorders.
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  • 158
    ISSN: 1432-2072
    Keywords: Nitrogen dioxide ; Prenatal exposure ; Behavior ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.
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  • 159
    ISSN: 1432-2013
    Keywords: Brown adipose tissue ; Cold-acclimation ; Noradrenaline turnover ; Oestradiol ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been shown previously that high plasma levels of oestradiol inhibit brown adipose tissue thermogenesis. Since rats and mice show a close association between thermogenic activity in and sympathetic discharge to brown fat, we measured the noradrenaline turnover in rats with high plasma levels of oestradiol to establish whether the observed inhibition of thermogenic activity is brought about by a reduction in the sympathetic drive to brown adipocytes. Oestradiol-filled Silastic capsules were implanted subcutaneously in female rats previously acclimated either to thermoneutrality or to cold. Control rats received empty implants. After 15 days treatment, noradrenaline turnover was measured by blocking its synthesis with α-methyl-p-tyrosine. As expected, noradrenaline turnover was higher in cold-acclimated rats than in rats kept at thermoneutrality. The presence of high plasma oestradiol levels did not alter sympathetic activity in any of the treated groups despite reducing thermogenic activity. This result reveals that oestradiol dissociates the thermogenic activity of brown adipose tissue from its sympathetic activation. Such dissociation has never been previously reported in rats, although it seems to be common in Syrian hamsters. However the causative factor in this species is unknown.
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  • 160
    ISSN: 1432-2013
    Keywords: Skeletal muscle ; Muscle damage ; Treadmill running ; Serum ; Enzymes ; Water content ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Male Wistar rats were made to run uphill on a treadmill 5.5° incline at 17 m min−1 for 4 h, and killed for muscle and serum sampling 2, 4, 12, 24, 48 or 96 h after the exertion. To estimate the degree of muscle damage,β-glucuronidase activity, total protein concentration, water content and morphology were examined in the red parts of quadriceps femoris (MQF) and soleus (MS) muscles, the distal white part of the rectus femoris muscle (MRF) and the superficial part of triceps brachii muscle (MTB). Simultaneous serum samples were assayed for creatine kinase (CK) activity and carbonic anhydrase III (CA III) concentration. Fibre swelling and interstitial oedema were detected in MS at 4 h and in MQF at 12 h and typical histopathological changes, including inflammation and fibre necrosis, in both muscles 12–96 h post-exertion.β-Glucuronidase activity, a quantitative marker of muscle damage, was increased in MS at 4 h, in MQF at 24 h and in MRF 48 h after the running. No increase occurred in MTB. Water and protein content increased or decreased respectively, faster in MS (2 h post-exercise) than in MQF (12 h) or MRF (12 h). Water content thus contributed to muscle damage by preceding the increase inβ-glucuronidase activity. Serum CK activity was increased 2, 4, and 48 h after the running. Changes in serum CA III concentration were rather similar to those in CK but were not significant. The increase in serum CK was not in concert with the necrotic events in the muscle but occurred considerably earlier (2 h vs. 12–24 h post-exercise). The second peak in CK, 48 h post-exercise (during the necrotic phase), was smaller than the first one. Our results show that serum CK activity is an inaccurate estimate of exercise-induced muscle damage as regards interpretation of the degree and the time course of pathological events in the muscle.
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  • 161
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    Mycopathologia 125 (1994), S. 33-39 
    ISSN: 1573-0832
    Keywords: Aflatoxin ; Lymphocytes ; Mice ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This investigation sought to determine whether splenic lymphocytes obtained from Balb/C mice exposed to aflatoxin B1 (AFB1) showed any ultrastructural changes which could account for the immunodysfunction attributable to aflatoxins. Lymphocytes obtained from Balb/C mice administered aflatoxin B1 in olive oil daily for three weeks were studied using both transmission and scanning electron microscopy. The lymphocytes demonstrated ultrastructural changes primarily in the mitochondria where marked internal dissociation of the cristae was revealed by transmission electron microscopy. All other cellular organelles were unaffected. No significant alterations in external structure were observed under scanning electron microscopy. The findings of this study indicate that AFB1 administration does not affect the surface topography of lymphocytes, but AFB1, by causing extensive mitochondrial damage, may affect the way in which these cells function. This could be a possible explanation for the immunodysfunction associated with AFB1.
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  • 162
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    Pflügers Archiv 426 (1994), S. 183-188 
    ISSN: 1432-2013
    Keywords: Hippocampus ; Corticosterone ; Adrenalectomy ; Local cerebral blood flow ; Diurnal rhythm ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study examined the effect of glucocorticoid manipulations on local cerebral blood flow in the hippocampus. We measured local cerebral blood flow in the hippocampus at 1-h intervals over a 1-day period in freely moving rats, by means of the H2 clearance method, before and after sham adrenalectomy, adrenalectomy or adrenalectomy with corticosterone replacement. We also measured local cerebral blood flow in the prefrontal cortex before and after adrenalectomy. Four weeks after the adrenalectomy, hippocampal blood flow at each time of day was an average of 47% greater than before the operation, showing diurnal variation as before. After the sham adrenalectomy or adrenalectomy with corticosterone replacement, hippocampal blood flow did not change significantly with respect to either its level or its diurnal variation. Local cerebral blood flow in the prefrontal cortex increased by only 19% after adrenalectomy. The present study demonstrates that adrenalectomy causes a remarkable increase in hippocampal blood flow, probably due to a lack of corticosterone.
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  • 163
    ISSN: 1432-2013
    Keywords: Glutamine synthetase ; Kidney ; Intestine ; Glutamine ; Ammonia ; Amino acids ; Metabolism ; Rat ; In vivo
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine (MSO). Renal glutamine and ammonia metabolism was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO-treated rats and their pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids were determined concomitantly. After 2 and 4 days of MSO treatment, arterial glutamine concentrations were reduced to 55%, while arterial ammonia concentrations increased by 70%. Kidney glutamine uptake reduced, but systemic pH was unchanged. Fractional extraction of glutamine remained unchanged, suggesting that also in vivo net uptake of glutamine by the kidney at subnormal levels is related to arterial glutamine concentrations. As a result, at day 2 but not at day 4, the kidney reduced the net release of ammonia into the renal vein and thus reduced net renal ammonia addition to body ammonia pools. Therefore at day 2, the kidney seems to play an important role in adaptation to both hyperammonaemia and hypoglutaminaemia.
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  • 164
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    Pflügers Archiv 426 (1994), S. 328-332 
    ISSN: 1432-2013
    Keywords: Cortical collecting duct ; K+ channel ; Rat ; Isolated tubule ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Ion channel current amplitudes (μ) and open probabilities (P o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of μ, P o, and mean dwell times (τ) of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K+ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The μ value of the intermediate-conductance K+ channel (i-K+) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean τ values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K+ (s-K+) channels, which were found in the same membrane patches as the i-K+, an accurate analysis of P o and τ was not possible with the SM. The μ value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P o was 16.6±4.6%, the open τ value was 11.1±2.8 ms, and the closed τ value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P o, and mean τ values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.
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  • 165
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    Pflügers Archiv 426 (1994), S. 351-353 
    ISSN: 1432-2013
    Keywords: Rat ; Brown adipose tissue ; Noradrenaline responsiveness ; Oxygen consumption ; Cold acclimation ; Body temperature ; Oxidative capacity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rectal temperature and oxygen consumption (üüO2) were monitored in female rats acclimated either to cold or to thermoneutrality and with and without chronic administration of oestradiol. The hormone is known to inactivate brown adipose tissue (BAT) and to reduce its response to noradrenaline (NA). The role of sympathetic control was studied by administering NA or the adrenergic blocker propranolol. Oestradiol treatment did not affect rectal temperature in the states of acclimation to thermoneutrality and to cold, nor did it change the hypothermic response of cold-exposed rats to temporary food deprivation. In the cold-acclimated rats, both controls and oestradiol-treated animals exhibited similar degrees of metabolic reduction after propranolol administration in the cold and similar degrees of metabolic activation by NA at thermoneutrality. Rats acclimated to thermoneutrality showed a larger metabolic response to NA when treated with oestradiol. The results suggest that oestradiol, while inactivating the BAT response to NA, activates the NA responsiveness of other metabolically active tissues in cold-induced thermogenesis. The observation of a greater oxidative capacity in the kidney and the rectus abdominis muscle of oestradiol-treated, cold-acclimated rats would be in line with this proposal.
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  • 166
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    Pflügers Archiv 426 (1994), S. 371-377 
    ISSN: 1432-2013
    Keywords: Body temperature ; Respiration ; Electrolytic lesions ; Urethrane anaesthesia ; Hypothalamus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Urethane-anaesthetised rats were exposed to hypoxia (7% O2 in N2) for 5 min periods while body core temperature (T bc) was maintained within the normal range (37–38° C) using an abdominal heat exchanger. Animals were exposed to hypoxia and after placement of electrolytic lesions in either the anterior (n=6) or posterior hypothalamus (n=6). Neither lesion altered respiration while rats breathed air at either T bc. At normal T bc, rats responded to hypoxia with increased ventilation throughout the exposure period. This response was unchanged by lesions in either location. At reduced T bc rats responded to hypoxia with an initial increase in ventilation followed by depression to below air-breathing levels. This depressive response was unchanged after anterior hypothalamic lesions but eliminated after posterior hypothalamic lesions. It is concluded that neurons either originating in the posterior hypothalamus, or passing through it, play a role in the interaction between cold and hypoxia which leads to inhibition of respiration.
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  • 167
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    European archives of oto-rhino-laryngology and head & neck 251 (1994), S. 267-270 
    ISSN: 1434-4726
    Keywords: Cochlea ; Ultrastructure ; Stria vascularis ; Development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mammalian stria vascularis undergoes certain developmental changes in the postnatal rat. The present study was designed to examine the ultrastructure of the stria vascularis in rat pups from immediately after birth to 20 days postpartum. The cochlea were removed with the animals under xylazine (Rompun) anesthesia and were prepared for transmission electron microscopy. Each of the three cell types in the stria were found to contain kinocilia up until 12–17 days of age. The presence of kinocilia in the intermediate and basal cells has not been previously described. Findings suggest that these organelles may serve a motile and/or sensory function to assist in the maturation of cell functions, particularly ion transport, during early stages of development.
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  • 168
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    Documenta ophthalmologica 87 (1994), S. 315-329 
    ISSN: 1573-2622
    Keywords: Experimental retinal detachment ; Glial fibrillary acidic protein ; Müller cells ; Oxygen ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We conducted an extensive histological study of the retinas of newborn rats that had been exposed to hyperoxic conditions. Our aim was to verify whether it is possible, using oxygen alone, to induce retinal detachment, a lesion that is characteristic of the more advanced stages of retinopathy of prematurity (ROP). Eight litters (total number of animals: 64) of newborn, albino Wistar rats were used. Four litters (32 rats) were exposed to 80% oxygen for the first ten days of life. Some of these rats were then removed to room-air environments where they were kept for two, three or four more weeks. The other four litters (32 rats) were maintained for the entire period in room-air. On the 11th, 25th, 32nd and 39th days of life rats from both the exposed and control groups were sacrificed and 5 micron sections of their in toto eyeballs were submitted to histological evaluation and immunohistochemical studies. Folding of the internal retinal layers was observed in some of the animals exposed to hyperoxia, as well as those kept in room air. These folds did not alter the overall thickness of the retina itself and were probably congenital. Retinal folds and microdetachments were seen in many of the retinas from the exposed group of rats. Extensive detachment was observed in one of the rats sacrificed after two weeks of room-air recovery, in two of those recovered for three weeks and in two exposed to four weeks of room air. The sections containing these areas of retinal detachment showed marked increases in glial fibrillary acidic protein (GFAP) in immunocytochemical studies, suggesting that Müller cells might play a role in the pathogenesis of retinal detachment.
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  • 169
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    Mycopathologia 128 (1994), S. 181-192 
    ISSN: 1573-0832
    Keywords: Aflatoxin B1 ; Embryo ; Mature ; Ultrastructure ; Zea mays L.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Mature maize (Zea mays L.) embryos were exposed to aflatoxin B1 (AFB1) concentrations ranging from 0.1 to 25 µg/ml for 9 days. With increasing toxin concentration above 2 µg/ml, primary root elongation of germinated embryos was progressively inhibited, to reach a maximum value of 81% at 25 µ/ml toxin. An ultrastructural investigation of the subcellular alterations induced following toxin exposure provided evidence of deteriorative changes in several compartments of the plant cell. Alteration in membrane integrity (e.g., the tonoplast, plasmalemma and inner mitochondrial membrane) was a frequent feature of many cells. Apparent fusion of vacuoles, incorporation of cytoplasmic components into vacuoles and intravacuolar membrane whorls might be interpreted as deteriorative alterations. The results are discussed in the light of ultrastructural findings for other plant systems exposed to similar AFB1 concentrations, as well as findings for animal systems.
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  • 170
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    Methods in cell science 16 (1994), S. 109-115 
    ISSN: 1573-0603
    Keywords: Animal model ; Neurofibroma ; Schwann cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Peripheral nerve sheath (PNS) neoplasms, primarily neurofibromas, schwannomas and maliganant schwannomas, are among the most common tumors in fishes. Model systems involving PNS tumors in fishes are also valuable because mammalian models of PNS tumors are rare. Schwann cells, the primary cell type suspected of neoplastic transformation in these tumors, have been difficult to culture. We describe techniques for culturing normal and neoplastic Schwann cells from fish. We also present methods for preparing cells on culture dishes for electron microscopy which are especially useful when specific cells in a culture must be located for ultrastructural examination.
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  • 171
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    Hydrobiologia 292-293 (1994), S. 137-142 
    ISSN: 1573-5117
    Keywords: Ultrastructure ; morphology ; integument ; copepoda ; crustacea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The integument of Parathalestris harpactoides (Claus, 1863) is studied by scanning and transmission electron microscopy. The general structure of the integument conforms to the common pattern known from Copepoda. Emphasis is given to the structural variation of the cuticle in different regions of the body. The cuticle measures about 6 µm in most parts of the body, and shows a laminate appearance. The epicuticle is about 60 nm thick. Numerous pore canals containing muscular tonofilaments penetrate the procuticular layer of the integument. A peculiar feature is the presence of a ‘honeycombed’ layer in the outermost zone of the cuticle of some parts of the body. The epidermal layer, muscle insertions and integumental pores are of common type. The cuticle of some specimens, both males and females, is covered with microorganisms.
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  • 172
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    Urological research 22 (1994), S. 51-55 
    ISSN: 1434-0879
    Keywords: Bladder dysfunction ; Muscle strip ; Rat ; X-irradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Strips of rat detrusor muscle were studied in an organ bath 6 months after X-irradiation at doses of 15 and 25 Gy; cystometric studies in these animals had shown a persistent and significant reduction in compliance. The organ bath study demonstrated an increase in the purinergie sensitivity of irradiated detrusor muscle as compared with control. This was significant: p〈0.0145 for the 25 Gy dose group (n=8) and p〈0.0456 for the 15 Gy group (n=8) at an α,β-methylene-ATP concentration of 10-4 M (Mann-Whitney U-Test). There was no difference in sensitivity to cholinergic or noradrenergic stimulation, or to electrical stimulation of the transmural nerves. The finding of purinergic hypersensitivity in irradiated muscle, coupled with ultrastructural evidence of a neural injury, raises the interesting possibility that a denervation super-sensitivity phenomenon may contribute to the pathophysiology of post-irradiation bladder dysfunction.
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  • 173
    ISSN: 1434-0879
    Keywords: Kidney ; Pyelonephritis ; Rat ; Sialidase (neuraminidase) ; Urokinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Renal stone formation can be caused by many different and varied disturbances, some of which are poorly understood. The relationship between urinary infection and renal stone formation has not been completely clarified. It is argued that renal stones form primarily as a consequence of the hydrolysis of urea by the bacterial enzyme urease. However, no explanation is given for microorganisms that produce urease only occasionally or not at all. The question arises as to wheter the infection-induced microorganisms might not be playing a double role in renal stone formation by not only producting urease, but also by affecting in vivo urokinase (UK) and sialidase (SA) activity. With this in mind, the effect of Escherichia coli on renal UK and SA activity has been studied in male rats with a normal diet. The renal UK (P=0.208) and SA (P=0.2135) activities did not differ significantly between the two kidneys of the same rat. In contrast, when drainage from one kidney of a rat was externally obstructed, the UK and SA activities differed significantly between kidneys (P〈0.015). An increase in UK (r=0.6456, P〈0.0001) and SA (r=0.7507, P〈0.0001) activity was observed over time in the obstructed kidney. Subcutaneous injections with E. coli reduced the UK activity of the obstructed kidney significantly (p=0.0171). However, the SA activity remained the same (P=0.3929). This decrease in the UK activity in the presence of microorganisms may result in an increase in the uromucoid concentration, leading to renal stone formation in the presence of increased salt precipitation on the uromucoid as caused by the urease producing microorganisms.
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  • 174
    ISSN: 1434-0879
    Keywords: GnRH-DT vaccine ; Testosterone ; Ultrastructure ; Rat ; Prostate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate the effects of active immunization against gonadotropin-releasing hormone (GnRH) on the ultrastructure of the rat ventral prostate, male Sprague-Dawley rats received three consecutive intramuscular injections of 10 μg/100g body weight (D-Lys6)-GnRH-diphtheria toxoid conjugate (GnRH-DT vaccine). Following immunization, test animals developed sufficiently high antibody titres to block the pituitary gonadal axis. Consequently testosterone values dropped to the levels in castrates. This therapy leads to atrophy of the prostate. Following immunization a strong immunological response, indicating the presence of considerable amounts of a GnRH-like peptide, was observed in the ventral prostates as early as 14 days after the first injection of GnRH-DT. Immunoneutralisation of GnRH-like activity may contribute to the effects observed.
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  • 175
    ISSN: 1434-0879
    Keywords: S100 protein ; Rat ; Carcinogenesis ; Renal neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Concentrations of α and β-subunits of S100 protein (S100-α and S100-β) in rat kidney neoplasms, including renal cell and mesenchymal tumors, were determined using a highly sensitive enzyme immunoassay, and both types immunohistochemically localized in tissue sections. Concentration of S100-α in each histological type of rat tumor were lower than in normal kidney, whereas levels of S100-β (mean±SE: 29.7±14.2 ng/mg protein, n=15) in renal cell tumors were significantly higher than in normal kidneys (0.55±0.06 ng/mg protein, n=7), or mesenchymal tumors (1.21±0.43 ng/mg protein, n=9). In normal rat kidney tissues S100-α was immunohistochemically positive in epithelial cells of the distal tubules, the thin limbs of loops of Henle, and the collecting ducts. No appreciable immunostaining for S100-β was found in any nephron segment. Both S100-α and S100-β were positive for renal cell tumors, indicating new appearance of the latter during renal carcinogenesis in rats.
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  • 176
    ISSN: 1573-7365
    Keywords: Hippocampus ; Slices ; Protein synthesis ; Ischemia ; Glutamate ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Protein synthesis was measured in hippocampal slices which were exposed to glutamate (1 mM or 10 mM) or which were deprived of glucose and oxygen (‘in vitro ischemia’) for 15 min. Glutamate at 1 mM, a concentration estimated to occur duringin vivo ischemia did not affect protein synthesis. Ten mM glutamate inhibited protein synthesis immediately after exposure (50% of control values) and reduced ATP levels to about 30% of the control. After two hours, slices fully recovered their protein synthesis and energy metabolism. The effect of 10 mM glutamate was not receptor-mediated, as NMDA, AMPA, or metabotropic receptor antagonists failed to block the glutamate effect. Immediately after ischemia, protein synthesis was reduced to 30% of control values, and 2 hours later it was still depressed to one-half of control values. Energy charge, however, recovered completely. Ischemic inhibition of protein synthesis was not reversed by glutamate receptor antagonists. The data indicate that inhibition of protein synthesis in hippocampal slices during ischemia is not glutamate-dependent.
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  • 177
    ISSN: 1439-6327
    Keywords: Hindlimb suspension ; Recovery ; Soleus muscle ; Fibre-type composition ; Myosin heavy-chain IId isoform ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the changes in myosin heavy-chain (HC) isoforms and fibre-type composition in rat soleus muscle using both myosin adenosine triphosphatase staining and sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE) analyses during the recovery period after 4 weeks of hindlimb suspension. Although there was no change in type IIc fibres after the suspension, an increase in this type of fibres was observed during the 1- to 4-week recovery period. The increase in type Ilc fibres was considered to be due to a shift from type Ila to IIc fibres. The SDS-PAGE analysis revealed the presence of the HC IId isoform, which was not observed in the control muscle, after a 4-week hindlimb suspension. The HC IId isoform gradually decreased over 3 weeks of recovery and disappeared in the 4th week of recovery after the suspension. These results suggest that the hypogravity conditions induced by hindlimb suspension stimulated the synthesis of the HC IId isoform, whereas an increase in mechanical load to the muscle accelerated the degradation of the HC IId isoform and the synthesis of type Ilc fibres during the recovery period after hindlimb suspension.
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  • 178
    ISSN: 1615-6102
    Keywords: α-Amylase ; (1-3, l-4)-β-Glucanase ; Hormones ; Monensin ; Transfection ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A procedure has been developed to isolate protoplasts from mature aleurone layers of the malting variety Alexis and four other barley genotypes. It combines induction of endogenous cell wall degrading enzymes together with use of Onuzuka cellulase R 10 and driselase and results in better yields for two varieties than can be obtained with the huskless variety Himalaya. The viability of the freshly isolated protoplasts is greater than 90% and in spite of the presence of gibberellic acid during isolation procedures, most of the protoplasts are at an early developmental stage, as judged by ultrastructure. Gibberellic acid-induced changes in protoplast structure resemble those reported for Himalaya protoplasts. The protoplasts secrete both α-amylase (EC 3.2.1.1) and (1-3, 1-4)-β-glucanase (EC 3.2.1.73) into the surrounding medium. Transfection studies using a low pI α-amylase promoter to direct chloramphenicol acetyltransferase expression in aleurone protoplasts from Alexis and Himalaya revealed significant differences in their hormone responsiveness. In the absence of hormones, low levels of expression of the reporter enzyme were obtained in Alexis protoplasts, while high levels were characteristic for Himalaya protoplasts. An 8-fold increase in the expression of the reporter gene was induced by supplying the transfected Alexis protoplasts with gibberellin A3, whereas expression in Himalaya protoplasts remained unchanged. When Himalaya protoplasts were isolated from aleurone layers that had not been incubated with GA3 during the initial stages of protoplasting (the classical procedure), the hormone response of the promoter was 2.5-fold. It is thus possible to optimize the aleurone protoplast isolation procedure for different barley genotypes and mutants of interest in studies of transgenic gene expression and hormone induced secretion of proteins from this unique secretory plant tissue.
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  • 179
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    Medical molecular morphology 27 (1994), S. 1-7 
    ISSN: 1860-1499
    Keywords: Medulloblastoma ; Primitive glioma ; Differentiation ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To increase our understanding of the differentiation potential and cytogenesis of embryonal tumors in the brain, 12 medulloblastomas and 10 primitive gliomas were studied by electron microscopy. Of the medulloblastomas, 6 cases were undifferentiated tumors that demonstrated fine processes similar to microspikes. The remaining 6 cases were poorly-differentiated tumors. Axon-like processes were seen in 4 of these cases, including one with dense core vesicles. Astroglial processes were seen in 4 cases. Of the primitive gliomas, there were 2 undifferentiated tumors and 8 poorly-differentiated tumors. Some of the undifferentiated tumor cells had broad cytoplasmic processes. Of the 8 poorly-differentiated gliomas, there were groupings of junctional complexes in 7, microvilli in 4 and bundles of intermediate filaments in 5. It is concluded that medulloblastomas have both neuronal and glial differentiation potentials and that primitive gliomas have only glial differentiation potential. The origin of medulloblastomas may be from the remnants of cell nests with a multipotential differentiation capacity, and the origin for primitive gliomas may be from remnants of glial precursor cells.
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  • 180
    ISSN: 1860-1499
    Keywords: Ultrastructure ; Transferrin receptor ; Oral malignant melanoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A rare variety of malignant melanoma in the maxilla was studied by electron microscopic observation and an immunohistochemical investigation of the transferrin receptor (TfR). A number of low-stage melanosomes were seen, and the TfR was found in both the cell membrane and the cytoplasm.
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  • 181
    ISSN: 1860-1499
    Keywords: Vasoactive intestinal polypeptide (VIP) ; Intestinal ischemia ; Immunohistochemistry ; Ganglionic cells ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alterations in the distribution of vasoactive intestinal polypeptide (VIP) in normal and ischemic small intestines of dogs were studied by using conventional transmission electron microscope, and immunohistochemistry for light and electron microscopy. At the light microscopic level, immunoreactivity was evident in the intestinal ganglionic cells of control segments. At the electron microscopic level using a pre-embedding method, the entire cytoplasm of the ganglionic cells in the control segments was filled with VIP immunoreactive products, while the post-embedding experiment showed positive reactions only within the VIP granules and Golgi vesicles. After 30 min of ischemia, immunoreactivity was greatly decreased in the ganglionic cells and a large amount of VIP immunoreactive product appeared in the striated border of epithelial cells and in nerve fibers of the subepithelial layer. These results suggest that intestinal ischemia might lead to the release of VIP, which seems to bind to the microvillus membrane of epithelial cells. The relationship between the changes in VIP distribution and its protecting mechanisms of ischemic damage is discussed.
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  • 182
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    Medical molecular morphology 27 (1994), S. 113-122 
    ISSN: 1860-1499
    Keywords: Breast cancer ; Apocrine carcinoma ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three cases of apocrine carcinoma of the breast were investigated by light and electron microscopy. Histologically, the tumor cells were shown to have eosinophilic granular cytoplasm and occasional cytoplasmic snouts protruding into the lumen. Ultrastructurally, light and dark tumor cells were identified, and there were many lysosome-like dense bodies of various sizes and small dense granules grouped in the subapical region. Many mitochondria with incomplete cristae and numerous small vacuoles were distributed in the cytoplasm. Occasionally, intracytoplasmic lumen were visible in the tumor cells. These ultrastructural findings are quite similar to those found in normal apocrine sweat glands. However, the presence of an intraductal component of carcinoma suggests the origin to be mammary epithelial cells.
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  • 183
    ISSN: 1860-1499
    Keywords: Human T-lymphotropic virus type I (HTLV-I) ; Ultrastructure ; Basedow's disease ; Lymphocyte ; Thyroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thyroid tissue from a patient with Basedow's disease and immunopositive for HTLV-I was examined. Histopathological and immunohistochemical studies revealed that follicular-epithelial cells (FEC) had papillary projections reaching into the follicular lumina which were associated with diffuse T, but not B, lymphocyte infiltration and occasionally formed aggregations intermingled with T and B lymphocytes. Ultrastructurally, infiltrated lymphocytes possessing round or irregularly indented nuclei were detected in the capillary lumen, stroma and, also, FEC layers. The lymphocytes extended irregular processes, attached to long thin processes of FEC and infiltrated into FEC layers. Cocultivation of minced thyroid tissue with normal lymphocytes resulted in the establishment of a type-C virus-producing T-cell line.
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  • 184
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    Medical molecular morphology 27 (1994), S. 159-164 
    ISSN: 1860-1499
    Keywords: NaOH digestion method ; Basal epithelial surface ; Calcium deposits ; Rat ; Scanning electron microscopy (SEM)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Basal surfaces of the rat corneal epithelium were studied by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The epithelium was dissociated from the underlying stroma by dissolving the basal lamina with NaOH, and its basal surface was observed by SEM. Depressions, produced by the indentations of the plasma membrane, were present on the basal cell surfaces in rats which were 15 and 18 months old. TEM observations clarified that electron-dense deposits, presumably containing calcium, were located in the depressions. These depressions also accompanied the thickened basal lamina.
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  • 185
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    Medical molecular morphology 27 (1994), S. 254-256 
    ISSN: 1860-1499
    Keywords: Gonad ; Mesonephros ; Histogenesis ; Primordial sex cord ; Folliculogenous sex cord ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The histogenesis and organogenesis of the human gonad in twelve embryos and six fetuses of ovulational ages 5 to 18 weeks was investigated by histological and ultrastructural examination, including observation of almost complete serial Epon-embedded sections of the entire gonads of 10 embryos. This investigation revealed that the main constituent cells of the gonads are derived from the mesonephros, and that the coelomic epithelium is not involved in the formation of the main component at any stage.
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  • 186
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    Medical molecular morphology 27 (1994), S. 260-263 
    ISSN: 1860-1499
    Keywords: Cellular interaction ; Follicular wall ; Granulosa cell ; Theca cell ; Ultrastructure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Bovine granulosa and theca cells were cultured on the opposite sides of a collagen membrane, and the morphological and structural effects of the interaction between theca and granulosa cells were studied. The apical surface of both granulosa and theca cells in the cocultured group appeared convex, while control cells were thin and flat. Numerous filopodia spread over the cellular surface connecting the cells. Constituents of rough endoplasmic reticulum in the cocultured cells were extended and swollen when compared with those observed in the cells cultured alone. Cocultured granulosa cells formed multilayered sheets, while granulosa cells cultured alone formed monolayered sheets. Theca cells in the cocultured group were more densely packed than cells cultured alone. These results indicate that the levels of cellular activity and intercellular communication among each type of cell are increased by the granulosa and theca cell interactions.
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  • 187
    ISSN: 1860-1499
    Keywords: X-ray microanalysis ; Freeze-drying ; Calcium ; Ultrastructure ; Isehemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is considerable interest of the changes in intracellular electrolytes in various pathophysiological states in cardiology. X-ray microanalysis is a useful method to measure the concentration of intracellular elements, and freeze-drying is a required technique for X-ray microanalysis to preserve elements. In this study, we utilized a new technique by which ultrathin sections were evaporated by carbon in an external freeze-dryer after freeze-drying and we were able to obtain clear electron micrographs of papillary muscles and myocytes. Calcium concentrations of mitochondria and cytosol were measured during 120 min ischemia. We showed that mitochondria played a role in intracellular calcium regulation during 30 min ischemia.
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  • 188
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    Molecular Reproduction and Development 37 (1994), S. 457-461 
    ISSN: 1040-452X
    Keywords: Canine sperm ; Pyospermia ; Ultrastructure ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: The red wolf (Canis rufus) is an endangered species with 194 individuals remaining in the wild and in various captive facilities. Breeding efforts at the Graham, WA site (Point Defiance Zoo and Aquarium) have involved artificial insemination with fresh or frozen semen in an effort to increase population and maximize the genetic potential of the stock. Electron microscopic observations were made in semen specimens obtained by electroejaculation from mature males prior to their use in an effort to determine semen parameters that might be useful in guiding breeding procedures. Sperm samples were either fixed immediately or treated with capacitating media and fixed after 4 to 7 hr of incubation. Many of the specimens examined were pyospermic (white cell in semen) and showed evidence of spermophagy, primarily by neutrophils. Of the six animals surveyed, only one showed little evidence of spermophagy, and three had extensive pyospermia and spermophagy but this finding was not correlated with fertility. Samples fixed immediately as well as those incubated for several hours showed evidence of spermophagy, indicating that the phagocytosis was not the result of culture. Gene pool restriction and/or captive stress may be contributing factors of reduced semen quality. © 1994 Wiley-Liss, Inc.
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  • 189
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    Microscopy Research and Technique 27 (1994), S. 145-164 
    ISSN: 1059-910X
    Keywords: Human ; Mouse ; Oocytes ; Maturation ; Ultrastructure ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: This paper reviews the process of peri-ovulatory oocyte maturation and the ultrastructural organization of the human egg and compares it with that of the mouse. The main thrust of the paper is on the human, since there are several reviews on the mouse. Both preovulatory and postovulatory events at fertilization, as well as some of the aberrant features of maturation are covered. Some changes induced by oocyte culture and cooling in the human are also included. The report attempts to focus on unique features of the human oocyte and shows a variety of ultrastructural differences between human and murine oocytes, which may well reflect differences in their physiology and biochemistry. Based on these differences and further observations on the process of fertilization of both species, particularly with respect to the inheritance of paternal centrioles, it is concluded that the mouse may not be a suitable modle for the development and refinement of current procedures in human assisted reproductive technology. © 1994 Wiley-Liss, Inc.
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  • 190
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    Microscopy Research and Technique 29 (1994), S. 211-218 
    ISSN: 1059-910X
    Keywords: Dopamine ; Locus coeruleus ; Rat ; Immunohistochemistry ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Dopaminergic innervation of the rat locus coeruleus (LC) was immunohistochemically studied by using monoclonal antibody directed against dopamine (DA) at the light- and electron-microscopic levels. A dense plexus of DA-immunoreactive (IR) varicose fibers was found not only in the cell body area of the LC but also in the dendritic area. Three hundred and forty DA-IR terminal boutons were observed. They were distributed in a wide range of diameters of 0.1-1.8 μm but most of them were large (mean value: 0.98 μm). Sixty-nine percent formed an asymmetric synapse. There were many axo-spinous connections. Small dendrites less than 0.3 μm in diameter displaying synaptic specialization were mostly dendritic spines (75%). Most of the target dendrites seemed to be noradrenergic in nature. It is suggested that dopaminergic innervation may play a powerful role in control mechanisms of activity of NA-containing neurons of the LC. © 1994 Wiley-Liss, Inc.
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  • 191
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    Microscopy Research and Technique 29 (1994), S. 411-431 
    ISSN: 1059-910X
    Keywords: Corrosion casts ; LM ; SEM ; TEM ; Microvasculature ; Ultrastructure ; Absorption ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: The aim of the present study was to provide a comprehensive morphological analysis of the porcine epididymis in view of the specific functions being performed in different regions of this organ. Blood supply and microvasculature of efferent ductules and epididymal duct were investigated by means of corrosion casts which were analysed macroscopically and by scanning electron microscopy. This revealed blood supply to the testis and epididymis to be closely related. The capillary pattern was typical for the efferent ductules, the caput, corpus, and distal cauda epididymidis, respectively. Corrosion casts were also used to visualize the course of the efferent ductules themselves. Tissue samples from different regions of the efferent ductules and epididymal duct were examined by light microscopy and both scanning and transmission electron microscopy, with special attention being payed to transitional areas. Morphological criteria allowed the distinction of three segments within the efferent ductules and of the initial segment, proximal caput, distal caput, corpus, proximal cauda, and distal cauda regions of the epididymal duct. Components of the endocytic apparatus of efferent ductule principal cells were identified by ferritin uptake. Ultrastructural evidence of absorption in the epididymal duct was particularly prominent in proximal and distal caput. Extensive cisternae of rough endoplasmic reticulum and a well-developed Golgi apparatus were indicative of active protein synthesis and secretion especially in the distal caput and corpus regions. However, assignment of various organelles in principal cells of the epididymal duct to either absorptive or secretory pathways still remains tentative. © 1994 Wiley-Liss, Inc.
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  • 192
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    Molecular Reproduction and Development 38 (1994), S. 421-430 
    ISSN: 1040-452X
    Keywords: Cumulus ; Oocyte ; Zona pellucida ; SEM ; Ultrastructure ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Surface characteristics of the bovine oocyte and its investments before, during, and after maturation, and fertilization in vitro were evaluated by scanning electron microscopy (SEM). Oocyte diameters were also measured during SEM analysis of the oocyte. The cumulus cells manifested a compact structure with minimal intercellular spaces among them in the immature oocytes. These became fully expanded with increased intercellular spaces after maturation in vitro, but contracted again after fertilization. The zona pellucida (ZP) showed a fibrous, open mesh-like structure in the maturing and matured oocytes. The size and number of meshes on the ZP decreased dramatically after fertilization. The vitelline surface of immature oocytes was characterized by distribution of tongue-shaped protrusions (TSPs) varying in density. After 10 and 22 hr of maturation incubation, oocyte surface microvilli (MV) increased to become the predominant surface structure, and TSPs decreased substantially. The vitelline surface of fertilized oocytes (at 6 and 20 hr) was similar to that of the matured oocytes, but unfertilized oocytes had less dense MV than did fertilized oocytes (at 20 hr). The diameter of the oocytes decreased from 99 to 80 μm during maturation and increased to 106 μm after insemination (P 〈 0.05). Membrane maturation was characterized by surface changes from a TSP-predominant pattern to a MV-predominant pattern. Thus, the bovine oocyte maturation process was found to involve the expansion of cumulus cells and the maturation of the ZP, which changes dramatically upon fertilization. Also, volumetric changes occurred in ooplasm processed for SEM following oocyte maturation and insemination. © 1994 Wiley-Liss, Inc.
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  • 193
    ISSN: 1059-910X
    Keywords: Rat ; Albumin ; Fibrinogen ; Immunohistochemistry ; Electromagnetic fields ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Biological effects of electromagnetic fields (EMF) on the blood-brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood-brain barrier after exposure to the various EMF-components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in: Resonance Phenomena in Biology, Oxford University Press, pp. 87-91].In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse-modulated with repetition rates of 8, 16, 50, and 200 s-1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg.The rats were not anesthetized during the 2-hour exposure. All animals were sacrificed by perfusion-fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3-4 minutes, and thereafter fixed in 4% formaldehyde for 5-6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. Albumin and fibrinogen were demonstrated immunohistochemically.The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P = 0.002). With pulsed 915 MHz microwaves with repetition rates of 200, 50, 16, and 8 s-1, 42 of 149 were positive, which is highly significant at the P = 0.001 level. This reveals that both CW and pulsed 915 MHz microwaves have the potential to open up the BBB for albumin passage. However, there is no significant difference between continuous and pulsed 915 MHz microwaves in this respect.The frequency of occurrence of extravasates (26%) was found to be independent of SAR for SAR 〈 2.5 W/kg, but rose significantly for the higher SAR values (to 43%).The question of whether the opening of the blood-brain barrier constitutes a health hazard demands further investigation. © 1994 Wiley-Liss, Inc.
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  • 194
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    Microscopy Research and Technique 29 (1994), S. 169-176 
    ISSN: 1059-910X
    Keywords: Celiac ganglion ; Chromaffin cells ; Autonomic nervous system ; Ultrastructure ; Guinea pig ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: Utilizing electron microscopic observation, several contacts between small, granule-containing cells (SGC) and postganglionic neurons (PGN) in the celiac ganglion of the guinea pig have been observed. A SGC in very close association with a PGN was seen to receive a distinct synaptic contact that contained many vesicles with dense cores. This contact was morphologically unlike cholinergic synapses previously reported on chromaffin cells. Because the SGC and PGN were clearly separated by a thin rim of satellite cell cytoplasm mutual to both cells, it is not known how or if the SGC would possibly exert a synaptic or paracrine effect on the PGN. Also, intraganglion SGC existed as large well-vascularized islands within the celiac ganglion. These intraganlion clusters sometimes contained more than 50 cells and perhaps could be considered to function as localized neuroendocrine components within the ganglion by secreting granule products into the nearby blood vessels for local or distant effects, although this certainly is not known. This work reports a unique synaptic ending upon a single-occurring SGC, which, in turn, closely approximates a ganglion neuron in a soma-somatic relationship. In addition, a very close association (but no actual contact) was observed between granule-containing processes, presumably emanating from the intraganglion clusters, and PGN. Whatever the function of ganglionic SGC may be, the exact relationship between SGC and PGN presumably would be of great interest and potential importance. © 1994 Wiley-Liss, Inc.
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  • 195
    ISSN: 1059-910X
    Keywords: Sinus afferent pathway ; SP interneurons ; Double immunocytochemistry ; Ultrastructure ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: The ultrastructure of substance P-containing nerve terminals synapsing on catecholamine neurons in the rat commissural subnucleus of the nucleus tractus solitarii (NTScom) was studied using a double immunocytochemical labeling technique. Although there were numerous tyrosine hydroxylase-immunoreactive (TH-I) somata present, substance P immunoreactive (SP-I) cell bodies were only occasionally found in the NTScom. At the light microscopic level, many SP-I terminals were seen closely associated with TH-I dendrites and somata. At the electron microscopic level, SP-I terminals synapsing on TH-I structures were also readily encountered. SP-I terminals contained small, clear, and predominantly spherical vesicles (32 ± 4 nm diameter), as well as large dense-cored vesicles approximately 100 nm in diameter. Postsynaptic TH-I dendritic profiles of various calibers and somata were encountered. These postsynaptic TH-I structures often showed postsynaptic densities. The morphological features of the SP-TH synapses in the present study, that is, the size of synaptic vesicles and the presence of postsynaptic densities, are quite different from those of central carotid sinus afferent synapses reported in our previous study [Chen et al. (1992), J. Neurocytol., 21:137-147]. Therefore, most of the SP terminals of the SP-TH synapses in the NTScom appear not to originate from the carotid sinus afferents. SP-I second-order neurons of the carotid sinus afferent pathway [Chen et al. (1991), J. Auton. Nerv. Syst., 33:97-98] may be one of the possible sources of such terminals. © 1994 Wiley-Liss, Inc.
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  • 196
    ISSN: 1439-6327
    Keywords: Carbohydrate loading ; Glycogen utilization ; Glycogen repletion ; Glycogen synthase ; Muscle ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently reported that rates of muscle glycogen repletion during the early period of recovery were increased by carbohydrate (CHO) loading in rats previously fed a high fat diet. However, the reason for this remained unanswered. The purpose of this study was to examine whether an increase of glycogen utilization due to an elevated pre-exercise glycogen store would enhance rates of glycogen repletion in muscle. Despite an equal degree of glycogen depletion, the rates of glycogen repletion of soleus, red and white gastrocnemius muscles by postexercise administration of glucose (3.0 g · kg−1 body mass) and citrate (0.5 g · kg−1 body mass) were faster in the CHO loaded (3 days) rats than in the nonloaded rats, as a result of elevated pre-exercise glycogen content and consequently the greater glycogen utilization. The higher rate of muscle glycogen repletion may in part be explained by increased postexercise glycogen synthase activity.
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  • 197
    ISSN: 1432-0878
    Keywords: Odontoclasts ; Resorption ; Predentine ; Ultrastructure ; Histochemistry ; TR-ACPase (tartrateresistant acid phosphatase) ; Deciduous teeth ; Shedding ; Human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Resorption by odontoclasts of a superficial nonmineralized layer of predentine that occurs in prior to the shedding of human deciduous teeth was studied by light and electron microscopy. As resorption of the tooth roots neared completion, multinucleate cells appeared on the predentine surface of the coronal dentine between the degenerated odontoblasts, excavated characteristic resorption lacunae in the nonmineralized predentine. These multinucleate cells had the same ultrastructural characteristics as odontoclasts and histochemical demonstration of tartrate-resistant acid phosphatase activity in the multinucleate cells revealed intense staining in numerous small granules identified as lysosomes. Occasionally, the multinucleate cells simultaneously resorbed both nonmineralized and calcospherite-mineralized matrix in the predentine. The study demonstrates that multinucleate odontoclasts can resorb nonmineralized predentine matrix in vivo, probably in the same way as they resorb demineralized organic matrix in the resorption zone underlying their ruffled border.
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  • 198
    ISSN: 1432-0878
    Keywords: C-PON ; Neuropeptide Y ; Neostriatum ; Immunocytochemistry ; Ultrastructure ; Erinaceus europaeus (Insectivora)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The present study provides light- and electronmicroscopic immunocytochemical data on the presence of neurons that are immunoreactive to the C-terminal flanking peptide of neuropeptide Y, C-PON, in the neostriatum of the hedgehog (Erinaceus europaeus). Positive neurons have mostly fusiform or round perikarya from which two to four poorly branched processes arise. Immunostained fibers and puncta are also evenly distributed throughout the neostriatum. Ultrastructurally, each neuron exhibits a deeply invaginated nucleus surrounded by abundant cytoplasm with a well-developed rought endoplasmic reticulum and Golgi apparatus. Positive neurons receive symmetric and asymmetric synapses from unlabeled terminals. The results of this study can be correlated with previous findings, as the C-PON-positive neurons of the hedgehog resemble medium-sized neostriatal neurons that are known to be local circuit neurons exhibiting C-PON in the rat. Thus, a high degree of C-PON neuronal system phylogenetic conservation and function can be postulated for the neostriatum of mammals.
    Type of Medium: Electronic Resource
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  • 199
    Electronic Resource
    Electronic Resource
    Springer
    Cell & tissue research 277 (1994), S. 87-95 
    ISSN: 1432-0878
    Keywords: Blood-brain barrier ; Anionic sites ; Larvae ; Septate junctions ; CNS ; Glia ; Ultrastructure ; Drosophila melanogaster (Insecta)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The blood-brain barrier ensures brain function in vertebrates and in some invertebrates by maintaining ionic integrity of the extraneuronal bathing fluid. Recent studies have demonstrated that anionic sites on the luminal surface of vascular endothelial cells collaborate with tight junctions to effect this barrier in vertebrates. We characterize these two analogous barrier factors for the first time on Drosophila larva by an electron-dense tracer and cationic gold labeling. Ionic lanthanum entered into but not through the extracellular channels between perineurial cells. Tracer is ultimately excluded from neurons in the ventral ganglion mainly by an extensive series of (pleated sheet) septate junctions between perineurial cells. Continuous junctions, a variant of the septate junction, were not as efficient as the pleated sheet variety in blocking tracer. An anionic domain now is demonstrated in Drosophila central nervous system through the use of cationic colloidal gold in LR White embedment. Anionic domains are specifically stationed in the neural lamella and not noted in the other cell levels of the blood-brain interface. It is proposed that in the central nervous system of the Drosophila larva the array of septate junctions between perineurial cells is the physical barrier, while the anionic domains in neural lamella are a “charge-selective barrier” for cations. All of these results are discussed relative to analogous characteristics of the vertebrate blood-brain barrier.
    Type of Medium: Electronic Resource
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  • 200
    ISSN: 1432-0878
    Keywords: Key words: C-PON ; Neuropeptide Y ; Neostriatum ; Immunocytochemistry ; Ultrastructure ; Erinaceus europaeus (Insectivora)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The present study provides light- and electron-microscopic immunocytochemical data on the presence of neurons that are immunoreactive to the C-terminal flanking peptide of neuropeptide Y, C-PON, in the neostriatum of the hedgehog (Erinaceus europaeus). Positive neurons have mostly fusiform or round perikarya from which two to four poorly branched processes arise. Immunostained fibers and puncta are also evenly distributed throughout the neostriatum. Ultrastructurally, each neuron exhibits a deeply invaginated nucleus surrounded by abundant cytoplasm with a well-developed rough endoplasmic reticulum and Golgi apparatus. Positive neurons receive symmetric and asymmetric synapses from unlabeled terminals. The results of this study can be correlated with previous findings, as the C-PON-positive neurons of the hedgehog resemble medium-sized neostriatal neurons that are known to be local circuit neurons exhibiting C-PON in the rat. Thus, a high degree of C-PON neuronal system phylogenetic conservation and function can be postulated for the neostriatum of mammals.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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