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  • 2015-2019
  • 1990-1994  (4,869)
  • 1920-1924
  • Engineering  (3,320)
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  • Immunohistochemistry  (654)
  • 101
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 99 (1994), S. 25-33 
    ISSN: 1432-1106
    Keywords: Regeneration ; Schwann cells Glial environment ; X-Irradiation ; Astrocytes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Exposure of the lumbar spinal cord of rats to X-rays 3 days after birth results in changes in the composition of central glia. Shortly after irradiation, there is both retardation of central myelin formation and a loss of integrity of the astrocyte-derived glia limitans on the dorsal surface of the cord. Subsequently, Schwann cells invade, undergo division and myelinate axons in the dorsal funiculi in the irradiated region of the cord, creating there an environment similar to that of peripheral nerve. The present study was undertaken to compare the ability of lesioned dorsal root axons to grow back into the altered glial environments that exist within the spinal cord after irradiation. This regrowth was assessed by injecting Fluoro-Gold into the spinal cord and subsequently examining neurons in the dorsal root ganglia (DRG) for the presence of this label. Numbers of retrogradely labeled neurons were counted in the DRG in both injured and contralateral non-injured sides. Non-irradiated control rats had almost no labeled DRG neurons on the injured side, whereas Fluoro-Gold labeled neurons were observed in substantial numbers in the DRG on the injured side of irradiated rats. There was a definite trend in the data, indicating that the longer the interval between irradiation and root injury, the greater the number of labeled neurons. Since the Fluoro-Gold labeling technique does not allow for visualization of the labeled axons within the spinal cord, a few animals were used to assess anterograde labeling with wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP/HRP) from the dorsal root into the spinal cord. HRP-filled regenerating axons were visualized in dorsal white and gray matter of the irradiated spinal cord. Such axons were not present in the non-irradiated spinal cords. Radiation-induced changes in glial populations are discussed, particularly with regard to the temporal sequence of these changes and their possible relationship to the conversion of a normally non-permissive environment into one conducive to axonal regrowth.
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  • 102
    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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  • 103
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 99 (1994), S. 205-213 
    ISSN: 1432-1106
    Keywords: Calcium-binding protein ; Development ; Immunocytochemistry ; Olfactory bulb ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The laminar development of the external plexiform layer (EPL) in the rat main olfactory bulb and the postnatal development of parvalbumin-immunoreactive [PV(+)] neurons mainly located in this layer were studied in animals at postnatal week 1–4 at a light microscopic level. The EPL in the adult olfactory bulb consists of two sublayers, the inner sublayer (ISL) and the outer sublayer (OSL). The ISL was already developed well even at postnatal day 7 (P7), whereas the OSL was first recognized at P10 as a thin zone consisting of more or less loosely packed large-sized and small-to-medium-sized somata subjacent to the glomerular layer (GL). The OSL increased in thickness and came to occupy nearly one-third to -half of the EPL at P14. PV(+) neurons first appeared at P10 mainly in the inner border of EPL. Only a few PV(+) neurons were scattered in the EPL at P10, but they increased remarkably in number during P14–21. Some of these PV(+) neurons at P10 had an intensely immunoreactive soma, extending relatively long processes with varicosities and/or spines. At P14, PV(+) neurons were located not only in the ISL but also at the border between the ISL and OSL, but in the OSL proper they were rarely observed. These PV(+) neurons showed branched and complicated processes with numerous varicosities and spines, displaying more mature features than those in previous stages. Even at P14 many of these PV(+) neurons appeared to exhibit some characteristic structural features of those in the adult stage. At P21, PV(+) neurons were observed in the OSL and thus showed almost the adult pattern in their distribution and morphological features. The present study showed the development of PV(+) neurons in the rat main olfactory bulb and the difference between the ISL and OSL of the EPL in postnatal development.
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  • 104
    ISSN: 1432-1106
    Keywords: Epilepsy ; GABA ; Noradrenaline Graft ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Gamma-aminobutyric acid (GABA)-releasing polymer matrices were implanted bilaterally, immediately dorsal to the substantia nigra, in rats previously kindled in the amygdala. Two days after implantation, rats with GABA-releasing matrices exhibited only focal limbic seizures in response to electrical stimulation, whereas animals with control matrices devoid of GABA had generalized convulsions. GABA release from the polymer matrices was high during the first days after implantation, as demonstrated both in vitro and, using microdialysis, in vivo. The anticonvulsant effect was no longer observed at 7 and 14 days at which time GABA release was found to be low. In a parallel experiment, polymer matrices containing noradrenaline (NA) were implanted bilaterally into the hippocampus of rats with extensive forebrain NA depletion induced by an intra-ventricular 6-hydroxydopamine injection. No effect on the development of hippocampal kindling was observed, despite extracellular NA levels exceeding those of rats with intrahippocampal locus coeruleus grafts that have previously been shown to retard kindling rate. The results indicate that GABA-releasing implants located in the substantia nigra region can suppress seizure generalization in epilepsy, even in the absence of synapse formation and integration with the host brain. In contrast, the failure of NA-releasing polymer matrices to retard the development of seizures in NA-depleted rats suggests that such an effect can only be exerted by grafts acting through a well-regulated, synaptic release of NA.
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  • 105
    ISSN: 1432-1106
    Keywords: Spreading depression ; Hypoglycemia ; Neuronal damage ; [Ca2+]e ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The calcium transients which are associated with spreading depression (SD) do not lead to neuronal necrosis, even if the SDs are repeated over hours. We have previously shown that a restriction of energy production by moderate hypoglycemia prolongs the calcium transients during SD. In the present experiments, we explored whether such prolonged transients lead to neuronal necrosis. To that end, SDs were elicited for 2 h by topical application of KC1 in anesthetized rats at plasma glucose concentrations of 6, 3, and 2 mM. The animals were then allowed to recover, and they were studied histopathologically after 7 days. In two other groups, hypoglycemic coma of 5 min duration (defined in terms of the d.c. potential shift) was induced either without or with a preceding train of SDs. These animals were also evaluated with respect to histopathological alterations. SDs elicited for 2 h did not give rise to neuronal damage when elicited at plasma glucose concentration of 6 mM, and, of the animals maintained at 3 and 2 mM, only a few animals showed (mild) damage. In general, therefore, repeated SDs with calcium transients of normal or increased duration fail to induce neuronal damage. The results suggest that, if calcium transients are responsible for a gradual extension of the infarct into the penumbra zone of a focal ischemie lesion some additional pathophysiological factors must be present, such as overt energy failure, acidosis, or microvascular damage. A hypoglycemia-induced calcium transient of 5 min duration gave no or only moderate neuronal damage. However, if a series of SDs were elicited in the precoma period, the damage was exaggerated. The results demonstrate that, normally, brain tissues can tolerate a hypoglycemic calcium transient of up to 5 min duration without incurring neuronal necrosis. They also demonstrate that calcium transients preceding a subsequent insult involving calcium influx into cells exaggerate the damage incurred. It is tentatively concluded that the “priming” transients alter membrane properties in such a way that cellular calcium homeostasis is perturbed.
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  • 106
    ISSN: 1432-1106
    Keywords: Medial amygdaloid nucleus (AME) ; Vasopressin ; Oxytocin ; Copulation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The medial amygdaloid nucleus (AME) occupies a central position in the circuitry that organizes sexual behavior in the male rat. It receives a projection from olfactory structures that are activated by pheromonal cues indicating receptivity in the female and projects in turn to limbic and hypothalamic structures that are thought to organize aspects of coitus. Electrical stimulation of the AME elicits a behavioral state that is indistinguishable by several measures from the post-ejaculatory interval. We used chronic single-unit recording techniques to determine the behavioral conditions in which the AME is normally active. We found that the cells indeed fired selectively during the presence of a receptive female, but that the discharge considerably anticipated copulation in time. We propose that sexual behavior in the male rat is a reaction chain of fixed action patterns, each one acting as a releaser for the next. The AME mediates an early event in the reaction chain, namely recognition of the receptive female, but electrical activation of the AME causes the reaction chain to proceed to its culminating behavior, the post-ejaculatory interval.
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  • 107
    ISSN: 1432-1106
    Keywords: Cuneate nucleus ; Cuneothalamic relay neuron ; Immunogold electron microscopy ; GABA-immunoreactive bouton ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigates the synaptic relation between γ-aminobutyric acid-immunoreactive (GABA-IR) and cuneothalamic relay neurons (CTNs) in the rat cuneate nucleus. Retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase complex (WGA-HRP) was used to label CTNs while anti-GABA immunogold serum was used for the detection of GABA-IR boutons associated with CTNs. With these procedures, immunogold-labelled GABA-IR boutons were found to form axosomatic, axodendritic and axospinous synapses with the WGA-HRP-labelled but immunonegative CTNs. Quantitative estimation showed that the mean ratios of GABA-IR to GABA-immunonegative boutons making synaptic contacts with somata, proximal dendrites, and distal dendrites were 47.9%, 49.1% and 34.7%, respectively. Statistical analysis showed that the incidence of GABA-IR boutons on the somata and proximal dendrites of CTNs was significantly higher than on the distal dendrites. Our results indicate that GABA is the primary inhibitory neurotransmitter in the cuneate nucleus, thereby emphasizing the importance of postsynaptic inhibition on cuneothalamic relay neurons.
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  • 108
    ISSN: 1432-1106
    Keywords: Sympathetic preganglionic neurons ; Cholera toxin ; Pelvic ganglion ; Dorsal commissural nucleus ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The cell morphology of sympathetic preganglionic neurons (SPNs) in the dorsal commissural nucleus was studied by the retrograde labeling technique using cholera toxin subunit B (CTb) as a tracer. A small amount of an aqueous solution of CTb was injected unilaterally into the major pelvic ganglion of the male rat. Labeled SPNs were detected immunohistochemically using anti-CTb antiserum. Most of the labeled SPNs were observed in L1 to L3, and a very small number in T13. They were observed bilaterally in the sympathetic nuclei, such as the intermediolateral cell column, intercalated nucleus and the dorsal commissural nucleus. A loose network of longitudinally or transversely oriented SPN dendrites was located within the dorsal commissural nucleus itself. The lateral margin of the dorsal commissural nucleus was roughly demarcated by longitudinally oriented dendrites. Together with the dendrites of the SPNs of the intercalated and intermediolateral cell column, laterally oriented dendrites of the dorsal commissural nucleus converged and formed the transverse dendritic bundles in the intermediate zone that connect the dorsal commissural nucleus and the intermediolateral cell column. The transverse dendritic bundles were arranged periodically. The axons of the SPNs in the dorsal commissural nucleus traveled laterally into the transverse dendritic bundles, then turned ventrally near the intermediolateral cell column, and finally entered the ventral funiculus. After rhizotomy of the ventral roots of the upper lumbar cord, labeled SPNs were found only on the side contralateral to the rhizotomy. The dorsal commissural nucleus appears as a compact single cell column, but our results clearly show that this nucleus actually consists of two adjacent parallel columns of cells.
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  • 109
    ISSN: 1432-1106
    Keywords: Synaptic transmission ; Brain slice ; Synapse ; Nitric oxide synthase ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical analysis of the localization of nitric oxide synthase-(NOS)-like immunoreactivity revealed the presence of this enzyme in a few neuronal cell bodies and in dendritic and axonal processes within the rat locus coeruleus (LC). Also cells in the pericoeruleus area were NOS-positive. Intracellular recordings were made from LC neurons in brain slices. Bath application of the NOS inhibitors nitro-l-arginine methyl ester (l-NAME) or N G-monomethyl-l-arginine (l-NMMA) potently enhanced the excitatory postsynaptic potential (EPSP) evoked by focal electrical stimulation of the slice. Hemoglobin, which binds extracellular NO, also enhanced the EPSP. This enhancement was reversed by coadministration of l-arginine, a precursor of neuronal nitric oxide (NO). Neither NOS inhibitors, l-arginine, nor hemoglobin had effects on the resting membrane potential or impedance. These results suggest a role for NO in synaptic transmission in the LC.
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  • 110
    ISSN: 1432-1106
    Keywords: Synapsin I ; In situ hybridization Northern blot ; Gene expression Postnatal brain development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Synapsin I is a synaptic phosphoprotein that is involved in the short-term regulation of neurotransmitter release. In this report we present the first extensive study of the developmental expression of its corresponding messenger ribonucleic acid (mRNA) by in situ hybridization and northern blot analysis in rat brain. Synapsin I mRNA showed pronounced differences in expression in different brain regions during postnatal development. The early expression of synapsin I mRNA in ontogenetically older regions such as the thalamus, the piriform cortex and the hippocampus coincides with the earlier maturation of these regions, in contrast to its later expression in ontogenetically younger areas such as the cerebellum and the neocortex. An intriguing expression pattern was found in the hippocampus. In all hippocampal subregions synapsin I mRNA expression increased from postnatal day (PND) 1 to 17. After PND 17, however, there was a marked dissociation between persisting high expression levels in CA3 and the dentate gyrus and a strong decline in synapsin I mRNA expression in CA1. The persistence of synapsin I in some adult rat brain regions indicates that it plays a part in synapse formation during plastic adaption in neuronal connectivities.
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  • 111
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    Springer
    Experimental brain research 99 (1994), S. 223-232 
    ISSN: 1432-1106
    Keywords: Functional map ; Orientation behavior ; Descending pathways ; Corticocortical connections ; Tract-tracing methods ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The afferent and efferent connections of the vibrissal area of the rat motor cortex (VMCx) were investigated by injecting Phaseolus vulgaris leucoagglutinin (PHA-L) or wheat germ agglutinin-horseradish peroxidase into the physiologically defined VMCx. The VMCx formed reciprocal connections with the primary and secondary somatosensory cortex, lateral and ventrolateral orbital cortex, retrosplenial cortex, and perirhinal cortex. These corticocortical afferents originated from cell bodies in layers II–III and V, and some afferents originated from cell bodies in layer VI of the primary sensory cortex. All of the VMCx efferents terminated in layers I and V or layers I–III and V. The VMCx also formed reciprocal connections with the ventrolateral, ventromedial and centrolateral nucleus, the lateral portion of the mediodorsal nucleus and the posterior complex of the thalamus. It projected bilaterally to the caudate putamen, primarily ipsilaterally to the superior colliculus, anterior pretectal nucleus, and pontine nucleus, and mainly contralaterally to the oral part of the spinotrigeminal nucleus and the reticular formation around the facial nerve nucleus. Finally, injections of PHA-L into the superior colliculus demonstrated that this structure projected contralaterally to the lateral part of the facial nerve nucleus. These data suggest that the VMCx plays a key role in sensorimotor integration, through its extensive interconnectivity with numerous brain structures, and may modulate orientation behaviors by relaying processed information to the superior colliculus.
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  • 112
    ISSN: 1432-1106
    Keywords: Hyperthermic treatment ; Apneic hypoxia ; Electroencephalogram ; Heat-shock protein ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Electroencephalography (EEG) was utilized for investigating the effect of hyperthermia followed by apneic hypoxia in rats. They were heated whole-bodily to 41° C for 15 min under the control of an artificial rodent ventilator, after drug-induced generalized paralysis. A transcutaneous oxygen saturation monitor was applied to detect the hypoxic condition. EEG was monitored with bipolar needle electrodes. The 72-kDa heatshock protein (HSP72) in brain was analyzed by sodium dodecyl sulfate-polyacrylamide electrophoresis, followed by immunostaining with an anti-HSP72 antibody. There was no difference in the time interval from onset of apneic hypoxia to flat EEG between the hyperthermic and control groups, but cortical electrical activity appeared earlier in the hyperthermia group than the control group, after 90 s of ventilation interruption. The cardiac function did not change in the two groups. The HSP72 synthesis significantly increased in the brain of the rats with hyperthermic treatment.
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  • 113
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    Springer
    Experimental brain research 99 (1994), S. 435-440 
    ISSN: 1432-1106
    Keywords: GABA ; Uptake ; Sexual differentiation ; Cell culture ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is involved in the control of sexually dimorphic brain functions, such as pituitary secretion and reproductive behavior. Hypothalamic GABAergic systems in vivo exhibit sexually dimorphic functional properties. Sexual dimorphisms in the rat brain are currently thought to be brought about by the organizational influence of gonadal steroids during the perinatal developmental period. The present study is concerned with the question of whether developing hypothalamic GABAergic neurons are primary targets of sex hormones. Since it is impossible to distinguish direct from indirect effects of experimental manipulations of the hormonal environment of the in vivo brain, sex-specific primary cultures raised from embryonic day 14 rat diencephalon and cultured for up to 8 days in vitro (DIV) were used as a model system. Effects of sex steroids were investigated on high affinity uptake of [3H]GABA. GABA transport was already mature at 3 DIV. [3H]GABA uptake was sensitive to inhibition by nipecotic acid and the transmitter was taken up by high affinity transport (K m=15.2 μM). Immunocytochemical preparations demonstrated extensive networks of GABA-immunoreactive fibers at 8 DIV. Concomitantly with the outgrowth of neurites, there was a marked increase in maximum uptake velocity (Vmax). No differences could be detected regarding cell numbers or uptake kinetics between cultures from male and female donors. Neither cell numbers nor GABA uptake were affected by short- and long-term treatment with estradiol-17β or testosterone. It appears that hypothalamic GABAergic neurons in vitro do not develop sex differences in cell numbers or GABA transport. Both parameters, which otherwise have proved to be good indicators of sexual differentiation of cultured neurons, are also unaffected by sex steroids. These results suggest that sex differences in GABAergic transmission seen in the developing and adult rat in vivo are generated by additional factors, such as afferent or efferent connections with other sexually dimorphic neurons.
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  • 114
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    Springer
    Experimental brain research 99 (1994), S. 524-528 
    ISSN: 1432-1106
    Keywords: Prefrontal cortex ; 6-Hydroxydopamine ; Dopamine ; Noradrenaline ; Reaction and movement times ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We examined the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (PFC) in rats on motor initiation and execution in a simple reaction time task. Reaction times (RT) and movement times (MT) were measured in trained rats on four preand postoperative days. Animals with 6-OHDA lesions were selectively impaired on motor initiation as measured by a significant increase in RT on each postoperative day. Motor execution was intact postoperatively, since MT was not altered. Neurochemical analysis revealed a significant depletion of prefrontal dopamine (DA) and noradrenaline (NA) in lesioned animals. It was concluded that DA and, to a lesser extent, NA in the rat PFC were involved in monitoring RT performance.
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  • 115
    ISSN: 1432-1106
    Keywords: Basal forebrain ; Nucleus basalis ; Auditory cortex ; EEG desynchronization ; Sensory plasticity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the relationships between cortical arousal and cholinergic facilitation of evoked responses in the auditory cortex. The basal forebrain (BF) was stimulated unilaterally, while cluster recordings were obtained simultaneously from both auditory cortices in urethane-anesthetized rats. The global electroencephalogram (EEG; large frontoparietal derivation) and the local EEG (from the auditory cortex) were recorded. The BF was stimulated at two intensities, a lower one which did not desynchronize the EEG and a higher one which did. Twenty pairing trials were delivered, during which a tone was presented 50 ms after the end of the BF stimulation. At low intensity, the pairing procedure led to a transient increase in the ipsilateral tone-evoked responses. At high intensity, the pairing increased the ipsilateral evoked responses up to 15 min after pairing. Such effects were not observed for the contralateral recordings. Systemic atropine injection prevented the facilitations observed ipsilaterally. BF stimulations alone did not induce any increased evoked response either at low or at high intensity. These results show (1) that a tone, presented while the cortex is activated by cholinergic neurons of the BF, evokes enhanced cortical responses, and (2) that the duration of this facilitation is dependent on the stimulation intensity. These results are discussed in the context of neural mechanisms involved in general arousal and cortical plasticity.
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  • 116
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    Springer
    Experimental brain research 97 (1994), S. 415-422 
    ISSN: 1432-1106
    Keywords: l-Glutamate and l-aspartate ; Neurotransmission ; High affinity uptake ; Na+-dependent binding ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Binding of [3H]l-aspartate to thaw-mounted coronal sections of frozen rat forebrain was strong in grey regions of telencephalon (neocortex, hippocampus and neostriatum), but it was weaker and unevenly distributed in diencephalon. At low nanomolar concentrations of ligand used in the present studies, [3H]l-aspartate binding was strongly inhibited by l-threo-3-hydroxyaspartate and l-trans-pyrrolidine-2,4-dicarboxylate, compounds known to be substrate/inhibitors of the high affinity uptake of l-glutamate and l-aspartate. None of the typical ligands for the glutamate and aspartate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), N-methyl-d-aspartate and kainate, produced a strong enough inhibition (only CNQX at 100 μM weakly inhibited) of the Na+-dependent [3H]l-aspartate binding to suggest that [3H]l-aspartate was bound to the receptor binding sites. Furthermore, the binding was absolutely dependent on the presence of Na+ in the incubation medium. It is concluded that [3H]l-aspartate is a ligand suitable for autoradiographic studies of the distribution of Na+-dependent, high affinity uptake of acidic amino acids in the central nervous system (CNS). However, feasibility of using [3H]l-aspartate as a specific marker of glutamatergic and/or aspartergic synapses in the CNS requires further investigation.
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  • 117
    ISSN: 1432-1106
    Keywords: Licking ; Oral behavior ; Electrophysiology ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study examined the relationship of single-neuron activity (n = 739), recorded from the lateral striatum of freely moving rats, to oral movements involved in licking single drops of liquid. Certain neurons (n = 74) fired specifically in relation to licking. Their firing rates increased during licking, but remained near zero in the absence of licking, throughout a full sensorimotor examination of the remainder of the orofacial area and all other body parts. Another category of neurons (n = 17) fired during licking but also fired in the absence of licking, during one or more other orofacial sensorimotor function(s). Lick-related neurons were located in the lateral striatum, throughout the entire anterior-posterior range studied (from +1.5 to -1.5 mm anterior-posterior, A-P, bregma = 0). Summed over the full A–P range, they were located significantly ventral to representations of the trunk and limbs. These findings extend the characterization of the somatotopic organization exhibited by lateral striatal neurons in the rat, to include representation of oral functions, consistent with converging evidence regarding the functional organization of the striatum.
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  • 118
    ISSN: 1432-1106
    Keywords: In vivo microdialysis ; Astrocytic reaction ; Gliosis ; Brain lesion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In vivo microdialysis is an established tool for sampling extracellular fluid compartments. However, microdialysis faces the problem that the implantation of the probe damages the microenvironment from which measurements are derived. In this study, we examined the expression of basic fibroblast growth factor mRNA and protein at the cellular level after implantation of a microdialysis probe into the dorsal hippocampus and found that 8 h after inserting the probe bFGF mRNA was markedly increased in a relatively large area centered around the probe, involving both the dorsal hippocampus and the overlying cerebral cortex, as revealed by radioactive in situ hybridization. Using nonradioactive in situ hybridization with digoxigenin-labelled riboprobes, combined with immunohistochemistry for glial fibrillary acidic protein we demonstrated that bFGF mRNA was exclusively increased in astrocytes at the probe insertion site. Using immunohistochemistry we also found that bFGF-like immunoreactivity was increased after implantation of the probe close to the lesion site, as shown by an increased number of bFGF immunoreactive nuclear glial profiles. These results provide evidence that the implantation of a microdialysis probe into the brain induces activation of bFGF gene expression in astrocytes associated with nuclear bFGF-like immunoreactivity. We conclude that lesion-induced effects have to be considered when evaluating microdialysis data, and that mechanical trauma to the brain will activate astroglial trophism, as seen from the increased density of astroglial profiles demonstrating bFGF mRNA and protein levels.
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  • 119
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    Experimental brain research 98 (1994), S. 298-304 
    ISSN: 1432-1106
    Keywords: Potassium channels ; Patch clamp ; Cerebellar granule cells ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Macroscopic potassium currents were studied in cell-attached and inside-out patches from rat cerebellar granule cells. They were related with transient IA type potassium channels. Currents activated rapidly at potentials higher than -40 mV and did not inactivate completely. The magnitude of the current diminished when the membrane patches were excised. No differences in the activation and inactivation properties were found between patches in the integral cells and cell free membrane patches. A biophysical description of the currents is presented.
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  • 120
    ISSN: 1432-1106
    Keywords: Electroshock ; Neuropeptides ; Immunocytochemistry ; In situ hybridization ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Increased levels of somatostatin (SS) and neuropeptide Y (NPY) have been demonstrated in the hippocampal formation after kindling. The increase might be specifically associated with kindling, or be an effect of repeated seizures per se. In order to separate these two components we studied the effects of repeated electroconvulsive shocks (ECS) on hippocampal SS-like and NPY-like immunoreactivity and SS mRNA and NPY mRNA in situ hybridization. ECS elicit seizures without having a demonstrable kindling effect. Rats were subjected to 10, 20, or 36 ECS (50 mA, 0.5 s), given as one shock per day, 5 days per week. One, 2 and 30 days after the last ECS, the rats were killed, together with sham-treated control rats, and processed for immunocytochemistry and non-radioactive in situ hybridization. There was a bilateral increase in SS-like and NPY-like immunoreactivity 1 and 2 days after the last ECS in the outer part of the dentate molecular layer. This is the terminal field of the hilar SS-containing and NPY-containing neurons, which displayed both increased immunoreactivity and hybridization signal of the cell bodies. There was also a bilateral de novo expression of NPY-like immunoreactivity in the mossy fiber system, but this was not accompanied by the appearance of a detectable NPY hybridization signal over the parent dentate granule cell bodies. The increase in SS-like immunoreactivity and hybridization signal was most pronounced in the rats that had received the largest number of ECS. This was not observed for the NPY-like immunoreactivity and hybridization signal, where the increase appeared similar after 10, 20 and 36 ECS. One month after the last ECS, both the SS-like and NPY-like immunoreactivity and the in situ hybridization signals had decreased towards normal levels. Since increased SS and NPY levels are also induced by repeated ECS, these changes are accordingly not specific to kindling-induced seizures. In a second experiment, the perforant path to the fascia dentata was transected 1 month prior to the ECS treatment. Removal of such major afferent input did not abolish the ECS-induced increase in hippocampal SS-like and NPY-like immunoreactivity, suggesting that the neuropeptide changes were not caused by afferent stimulation via the perfant path fibers, but rather may be an effect of direct electrical activation of the relevant cells.
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  • 121
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    Experimental brain research 98 (1994), S. 391-400 
    ISSN: 1432-1106
    Keywords: Optokinetic nystagmus ; Vestibulo-ocular reflex ; Frontal eye field ; Hemineglect ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Spontaneous saccadic orientation and compensatory eye movements in response to optokinetic and vestibular velocity steps were studied in head-restrained, pigmented rats before and 1–2 weeks after unilateral ablation of the frontal eye field (FEF). One group of rats (n=5) received a deep lesion and another group of rats (n=4) received a superficial lesion of the left FEF. Postoperative response parameters such as the duration of slow buildup of eye velocity, the steady state velocity gain, the duration of optokinetic afternystagmus and of per- and postrotatory vestibular nystagmus were similar in the two groups of rats and did not differ from preoperative values measured in the same individuals. Superimposed upon these velocity components of nystagmus was a transient orienting response that expressed itself by a shift of the beating field of nystagmus in quick phase direction (gaze shift). The amplitudes of this gaze shift in quick phase direction were asymmetric in rats with a deep FEF lesion. Gaze shift amplitudes toward the side of the lesion were significantly enhanced and gaze shift amplitudes toward the intact side were significantly reduced. Similar asymmetries were observed in the distribution of spontaneous orienting movements of these rats in the light. Spontaneous saccadic eye movements of the same animals in darkness, however, were symmetric in amplitude to either side. These deficits suggest a partial sensory hemineglect after a deep unilateral lesion of the FEF and an involvement of this structure in the selective attention for targets in visual space. Thus the FEF orients the gaze at rest by means of saccades toward points of interest and during simulated circular locomotion by means of a shift of the beating field of nystagmus toward the visual sector that will be approached next.
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  • 122
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    Experimental brain research 99 (1994), S. 1-6 
    ISSN: 1432-1106
    Keywords: Nilvadipine ; Ca2+ entry blocker Focal cerebral ischemia ; Therapeutic effect ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study was conducted to invetigate the therapeutic effects of nilvadipine, a Ca2+ entry blocker, on rat focal cerebral ischemia. Under halothane anesthesia, a 3-0 nylon thread was introduced into the neck internal carotid artery to occlude the left middle cerebral artery. Either nilvadipine (3.2 mg/kg) or vehicle was administered subcutaneously 1, 2, 3, 4, 5 and 6 h following the occlusion (groups 1–6, respectively). Twenty-four hours after the occlusion, the percentage infarct volumes in nilvadipine-treated animals in groups 1–3 (21±11%, 24±11%, and 26±7%, respectively) were smaller than those in the respective control groups (36±5%, 35±3%, and 35+3%; P〈0.05). Compared with controls, the infarct size of the periphery of the fronto-parietal cortex decreased in nilvadipine-treated animals. The results indicate that nilvadipine decreases the size of infarction when administered up to 3 h after an ischemic insult. Thus, nilvadipine can be considered a potential therapeutic agent for acute focal cerebral ischemia, and may be clinically useful in stroke patients.
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  • 123
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    Experimental brain research 99 (1994), S. 191-204 
    ISSN: 1432-1106
    Keywords: Calcium-binding protein Immunocytochemistry ; Olfactory bulb ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The laminar distribution and morphological features of parvalbumin-immunoreactive [PV(+l)] neurons, one of the subpopulations of GABAergic neurons, were studied in the rat olfactory bulb at a light microscopic level. In the main olfactory bulb of adult rats, PV(+) neurons were mainly located in the external plexiform layer (EPL), and a few were scattered in the glomerular layer (GL), mitral cell layer (ML), and granule cell layer (GRL); whereas PV(+) neurons were rarely seen in the accessory olfactory bulb. The inner and outer sublayers of the EPL (ISL and OSL) appeared to be somewhat different in the distribution of PV(+) somata and features of PV(+) processes. PV(+) somata were located throughout the OSL, and PV(+) processes intermingled with one another, making a dense meshwork in the OSL; whereas, in the ISL, PV(+) somata were mainly located near the inner border of the EPL, and PV(+) processes made a sparser meshwork than that in the OSL. PV(+) neurons in the EPL were apparently heterogeneous in their structural features and appeared to be classifiable into several groups. Among them there appeared five distinctive types of PV(+) neurons. The most prominent group of PV(+) neurons in the OSL were superficial short-axon cells, located in the superficial portion of this sublayer and giving rise to relatively thick processes, in horizontal or oblique directions, which usually bore spines and varicosities. Another prominent group of PV(+) neurons extended several short, branched dendrites with spines and varicosities, which appeared to intermingle with one another, making a relatively small, spherical or ovoid dendritic field around the cell bodies; most of them resembled Van Gehuchten cells reported in previous Golgi studies. A third distinctive and most numerous group of PV(+) neurons were of the multipolar type; their somata and processes were located throughout the EPL. Their relatively smooth processes with frequent varicosities and a few spines were extended horizontally or diagonally throughout the EPL. A fourth group, which could be a subtype of the multipolar type, were located in or just above th ML and extended several thin, smooth dendrites in the EPL, some of which appeared to reach the border between the GL and EPL. Occasionally, axonlike processes arose from their cell bodies and extended into the ML. This fourth type of PV(+) neuron was named inner short-axon cells. A fifth group of neuron was located in the ML; processes of these neurons were extended horizontally, so they were named inner horizontal cells. PV(+) processes from the fourth and the fifth group of cells appeared to make contacts on mitral cell somata. In the GL some presumably periglomerular cells were also PV(+). In the GRL, PV(+) neurons were small in number, but they were also heterogeneous in their structural features; Some were identified as Golgi cells. This study shows a tremendous heterogeneity in morphological features of a chemically defined subpopulation of GABAergic interneurons in the olfactory bulb.
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  • 124
    ISSN: 1432-1106
    Keywords: HRP ; Sensory endings ; Vibrissae ; Nucleus caudalis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Peripheral and central terminations of mystacial pad afferents in rats were labeled by anterograde transport of wheat germ agglutinin-HRP (WGA-HRP) or choleragenoid HRP (B-HRP). Tracer was injected in the trigeminal ganglion and survival times were 6–24 h. Most of the innervation previously observed with other techniques in the mystacial pad were labeled by at least one of the tracers. This included extensive reticular endings from large-caliber afferents and a loose network of fine-caliber axons in vibrissal follicle-sinus complexes (F-SCs). Also included were individual highly branching bush-like profiles in the intervibrissal epidermis that arose from fine to medium caliber afferents. Other endings were revealed, such as beaded endings affiliated with tylotrich hairs and presumptive encapsulated lamellated endings affiliated with both vibrissae and small sinus hairs. Finally, the anterograde labeling also revealed differences in the branching pattern of Merkel afferents to the rete ridge collars and ring sinuses of F-SCs. Each tracer produced different patterns of labeling related to the survival time in the mystacial pad which corresponded to particular patterns of labeling in the trigeminal nucleus caudalis. WGA-HRP produced dense labeling of all types of afferents and peripheral endings as well as all laminae of nucleus caudalis after short survivals, but the labeling diffused as the survival times were increased. B-HRP preferentially filled the largest afferents and endings after shorter survivals, while smaller profiles became progressively labeled after longer survivals. In nucleus caudalis, profiles extending into laminae III, IV and inner part of lamina II were labeled with B-HRP after shorter survivals, but the outer part of lamina II also became labeled with longer survivals. This has not been previously observed with B-HRP. Along with other recent findings, these results reveal that the innervation of the mystacial pad especially by fine-caliber axons is far more extensive and complex than previously described. Also, depending on the survival time, the central and peripheral labeling patterns differ, which must be taken into account when interpreting results using these two tracers.
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  • 125
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    Experimental brain research 79 (1994), S. 444-452 
    ISSN: 1432-1106
    Keywords: Norepinephrine ; Lateral geniculate nucleus ; Locus coeruleus ; Burst firing ; Receiver operating characteristic analysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Neurons in the locus coeruleus (LC) encode information related to behavioral state in a tonic pattern of firing and information related to the occurrence of a sensory stimulus in a phasic pattern of firing. The effects of phasic stimulation of the LC (6 pulses at 30 Hz), designed to approximate its physiological activation by sensory stimuli, were studied in the lateral geniculate nucleus (LGN) of anesthetized rats. Phasic stimulation of the LC significantly increased neuronal firing in the LGN with a mean latency 320 ms from onset of stimulation. Receiver operating characteristic analyses on a trial-by-trial basis showed that phasic LC stimulation can result in a highly discriminable signal in the LGN. This increased neuronal firing rate in the LGN was specific for the site of stimulation and was reduced by the norepinephrine synthesis inhibitor α-methyl-p-tyrosine and by intravenous WB-4101 (α1-receptor antagonist). Neurons in the LGN have a single-spike firing mode when sensory information is faithfully relayed from retina to cortex and a burst-firing mode when the transfer of this information is degraded. Phasic LC stimulation reduced burst firing (2–5 ms interspike intervals, ISIs) at low frequencies (≤4 Hz) in the LGN, and for some neurons there was an absolute decrease in burst-like ISIs after LC stimulation, despite an increase in mean firing rate.
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  • 126
    ISSN: 1432-1106
    Keywords: Dopaminergic grafts ; Neuropeptide Y ; Ultrastructure ; Striatum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In a previous study we demonstrated that grafted dopamine (DA) neurons are able to induce an early and widespread normalization of DA-neuropeptide Y (NPY) interactions in the host striatum previously deprived of its DA input. Since similar recoveries were found to occur in striatal areas densely or poorly reinnervated by the graft, the question was raised as to what mechanisms (synaptic or volumic release) were involved in these functional effects. Ultrastructural analysis of graft-to-host relationships was performed using single — and double — immunolabelling techniques to detect neurons containing tyrosine hydroxylase (TH) and NPY, with a view to analysing the early establishment of synaptic connectivity in various areas of the host striatum. Within 1 month of the grafting, TH-immunoreactive (TH-IR) neurons showed most of the normal intrinsic morphological features characteristic of adult rat neurons and were found to have established direct relationships with various striatal neuronal populations. TH-NPY relationships were observed only in the area most densely reinnervated by the graft, and their relative frequency was found to be roughly the same as that determined in the intact striatum. Three months after the grafting, this percentage decreased, probably owing to the further elongation in TH-IR axons resulting in a wider distribution of the TH-NPY associations over the host striatum. In the zones distal from the graft, the reinnervation was far from complete and the few TH-IR fibres projected only to some unlabelled elements, mainly of the spiny type, which have been shown to interact normally with both DA afferents and NPY cells and therefore may relay the DA action over the whole striatum on the NPY population. It can be concluded from these data that the rapid and extensive functional normalization of the TH-NPY interactions previously found to occur in the entire striatum may depend on the restoration of direct and indirect synaptic relationships. A diffuse action of DA through non-synaptic mechanisms may also account for the fact that the amine has access to broader striatal populations than to those presumably reached by DA fibres arising from the graft.
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  • 127
    ISSN: 1432-1106
    Keywords: Immunohistochemistry ; Brain proteins ; ChAT ; GFAP ; Memory ; Astrocytes ; “Cholinergicrich” transplants ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In adult, lesion-impaired rat brain receiving embryonic day 15 (E15) fetal transplants, the level of expression of glial fibrillary acidic protein (GFAP) correlates positively with choline acetyltransferase (ChAT) levels and also with measurements of successful behavioural recovery. These results suggest that glial cells may play a pivotal role in the cognitive success of socalled cholinergic-rich transplants.The objective of this study was to investigate the association between GFAP-and ChAT-staining antigens in or around cholinergicrich fetal grafts transplanted in adult cortex. An immunohistochemical fluorescent double-labelling technique was used to simultaneously identify GFAP- and ChAT-staining cells to assess whether there was a different type or distribution of cells present in these successful transplants. On brain sections of transplant area, GFAP-staining glial cells did not co-label with ChAT-staining cells. The transplant area, therefore, did not reveal a different type of cell from those seen in comparable normal cortical brain but rather a greater concentration of both GFAP- and ChAT-positive staining cells.
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  • 128
    ISSN: 1432-1106
    Keywords: Seizures ; Ischemia ; Aminergic Neurotransmitters ; Microdialysis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The temporal profiles of aminergic neurotransmitter levels and of their acid metabolites after transient global cerebral ischemia in awake rats with and without subsequent seizures were compared using a microdialysis approach. In seizure animals, the post-ischemic levels of dopamine and serotonin were higher than the levels observed in the non-seizure controls. Inversely, the levels of the three neurotransmitter metabolites increased rapidly in the controls but not in seizure animals, where they remained at the low levels observed during and immediately after ischemia. This particular pattern is similar to that observed in rats submitted to prolonged ischemia or pretreated with monoamine oxidase inhibitors. In the seizure animals, neurotransmitter metabolites remained at low levels, as if the hypoxia had continued after the period of ischemia, inhibiting monoamine oxidase activity and, perhaps, neurotransmitter recapture.
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  • 129
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    Experimental brain research 99 (1994), S. 214-222 
    ISSN: 1432-1106
    Keywords: Afterhyperpolarization ; Motoneuron ; Locomotion ; In vitro ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Motoneuron afterhyperpolarization (AHP) amplitude and somatic input conductance were monitored during pharmacologically induced, locomotorlike ventral root activity using an isolated neonatal rat spinal cord preparation (transected at the C1 level). Nonspontaneously firing motoneurons were selected for study. Single spikes were evoked at regular intervals by brief depolarizing current pulse injections, while somatic input conductance was monitored by hyperpolarizing current pulses. The induction of rhythmic ventral root activity was associated with tonic depolarization of motoneurons as well as superimposed rhythmically alternating membrane depolarization and hyperpolarization (locomotor drive potentials, LDPs). In 9 of 13 trials (six of eight cells) the peak amplitude of AHPs following current-evoked action potentials was reduced during both the hyperpolarized and the depolarized phases of the LDP, compared with the pre-locomotor condition. The peak AHP amplitude increased during the depolarized phase of the LDP in 4 of 13 trials (three of eight cells); however, in 3 of these 4 trials measurement of the AHP later in the course of its trajectory, using a half decay time (HDt) reference point, demonstrated AHP amplitude reduction during rhythmic activity compared with the prelocomotor condition. In seven of eight motoneurons the induction of rhythmic activity was associated with a decrease in input conductance. The pattern of AHP amplitude and conductance modulation during the two phases of the LDP was consistent for individual trials; however, there was considerable intertrial variation. The results suggest that AHP modulation during locomotor-like activity in this preparation can be mediated independently of supraspinal influences by intrinsic spinal cord mechanisms, and the observed AHP suppression does not appear to be the passive result of an increase in background conductance. The discrepancy between peak and HDt-based AHP amplitude measurements during the depolarized phase of the LDP in some trials may be due to competing effects of passively enhanced potassium currents and a mechanism that actively reduces the calcium-dependent potassium conductance. The possibility that both the AHP amplitude and the input conductance changes observed during locomotor-like activity reflect a regulation of potassium channels is discussed.
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  • 130
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    Experimental brain research 99 (1994), S. 455-463 
    ISSN: 1432-1106
    Keywords: Caudal medulla oblongata ; Spinal Dorsal horn ; Cholera toxin subunit B ; Antinociception ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The location of neurons in the caudal medulla oblongata that project to the superficial or deep dorsal horn was studied in the rat, by means of retrograde labelling from confined spinal injection sites. The tracer cholera toxin subunit B was injected into laminae I–III (fuve rats) or I–V (three rats) at C4–7 spinal segments. Neurons projecting to the superficial dorsal horn were located in the dorsomedial part of the dorsal reticular nucleus ipsilaterally, the subnucleus commissuralis of the nucleus tractus solitarius bilaterally, and a region occupying the lateralmost part of the ventrolateral reticular formation between the lateral reticular nucleus and the caudal pole of the spinal trigeminal nucleus, pars caudalis, bilaterally. Neurons projecting to the deep dorsal horn, which were only labelled when laminae I–V were filled by the tracer, occurred in the dorsomedial and ventrolateral parts of the dorsal reticular nucleus and in the ventral reticular nucleus bilaterally. A few cells were located in the above described lateralmost portion of the ventrolateral reticular formation bilaterally and in the ventral portion of the ipsilateral cuneate nucleus. In the light of previous data demonstrating that dorsal horn neurons project to the dorsal reticular nucleus, the ventrolateral reticular formation, and the nucleus tractus solitarius, and that neurons in these three medullary regions are involved in pain inhibition at the spinal level, the descending projections demonstrated here suggest the occurrence of spino-medullary-spinal loops mediating the analgesic actions elicited in each nucleus upon the arrival of nociceptive input from the dorsal horn.
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  • 131
    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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  • 132
    ISSN: 1432-1106
    Keywords: Nerve growth factor ; NGF mRNA ; Sciatic nerve crush ; Dorsal root ganglia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The amount of nerve growth factor (NGF) in the L5, L6, and cervical dorsal root ganglia of rats was examined from 1 to 30 days after a unilateral crush lesion of the sciatic nerve and adjacent branches of the lumbar plexus at the level of the sciatic notch. Unilateral nerve crush produced increases in NGF content of lumbar ganglia at 1, 4, and 7–8 days after injury, with increased NGF mRNA at 4 and 7–8 days. Increases in NGF at 1 and 4 days were most pronounced on the unlesioned side while increases at days 7 and 8 were most pronounced on the lesioned side. NGF content increased in cervical ganglia of nerve-lesioned animals at 3 and 7 days after injury and in lumbar and cervical ganglia of sham-operated animals 3–5 days after surgery, with no comparable changes in NGF mRNA. Elevations of ganglionic NGF coincide temporally with some of the alterations in metabolism and morphology which occur in dorsal root ganglion neurons after sciatic nerve crush. However, the bilateral nature of increases in NGF demonstrates that the factor(s) producing the response is not restricted to ganglia axotomized by the injury. The data suggest that ganglionic NGF may be regulated by systemic factors, produced during stress or trauma, as well as by factors from the denervated target tissue and/or regenerating axons.
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  • 133
    ISSN: 1432-1106
    Keywords: Amygdala ; Estrogen ; Preoptic area ; Septum ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Electrical stimulation of the medial amygdala (AMY) elicited antidromic action potentials in neurons in the preoptic area (POA) and the lateral septum (LS) of 36 urethane-anesthetized ovariectomized female rats, which were either treated with estrogen o not treated. The extracellular potentials from the two sites showed similar characteristics, with the exception of the sensitivity to estrogen: they had latencies between 3 and 35 ms. Thresholds were as low as 100 μA. The mean relative refractory period was 2.2 ms. The peak-to-peak amplitudes of the positive-negative biphasic potential ranged from 1.0 mV to 12.0 mV. Estrogen had site-specific effects on parameters of antidromic activation in the POA. Estrogen-treated rats had a significantly higher threshold (937 vs 664 μA) and a longer refractory period (2.5 vs 2.1 ms) than the ovariectomized rats (P 〈 0.05 for each). The effects were absent in the LS. Selective cutting of the stria terminalis diminished the AMY-induced antidromic responses in the POA and LS. Electrical stimulation of the stria blocked the AMY-induced antidromic potentials by collision. Thus, estrogen-sensitive POA efferents as well as non-estrogen-sensitive LS efferents project to the AMY via the stria terminalis. Reductions in axonal excitability would inhibit neural conduction and transmission. Estrogen may therefore reduce the AMY inputs from the POA, without affecting those from the LS. Such alterations in the neural impulse flow may underlie estrogen-dependent neuroendocrine or behavioral regulation.
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  • 134
    ISSN: 1432-1106
    Keywords: Respiratory control ; Phrenic nerve ; Motoneuron ; Spinal hemisection ; Serotonin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serotonin reveals ineffective (subthreshold) pathways from the C2 lateral funiculus to ipsilateral phrenic motoneurons in spinalized rats. The objective of the present study was to investigate serotonergic modulation of crossed-spinal pathways to contralateral phrenic motoneurons. Rats (n = 10) were anesthetized (urethane), paralyzed, vagotomized, and artificially ventilated. The spinal cord was hemisected at C1–C2 and, on the intact side, a tungsten stimulating electrode was placed ventral to the C2 dorsal root entry zone in the dorsolateral (∼ 1.1 mm) or the ventrolateral funiculus (∼2.2 mm depth). Single shocks (100–750 μA, 0.1–0.5 ms, 2 Hz) elicited a short-latency (∼ 1.0 ms to peak) excitation in the ipsilateral phrenic nerve, but usually evoked little or no response in the contralateral phrenic nerve at either stimulus site. Following systemic injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) and the serotonin precursor 5-hydroxytryptophan (5–10 mg/kg), complex responses were revealed in the contralateral phrenic nerve, including; (1) spontaneous tonic activity; (2) a short-latency (∼1.0 ms to peak) evoked excitation; and (3) two long-latency (∼2.2 and 7.8 ms to peak) evoked excitations. The longest latency excitation was expressed only when the stimulating electrode was positioned in the dorsolateral funiculus. Contralateral evoked responses were blocked by systemic methysergide (2–6 mg/kg), a broad-spectrum serotonin receptor antagonist. These results indicate that serotonin converts ineffective crossed phrenic pathways in the spinal cord to effective pathways. It remains to be determined whether serotonin is both necessary and sufficient in this modulatory process, or if it is a nonspecific result of increased phrenic motoneuron excitability.
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  • 135
    ISSN: 1432-1106
    Keywords: Hippocampal formation ; Parahippocampal cortex ; Perforant pathway ; Limbic system ; Neuroanatomy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relations between the inputs from the presubiculum and the parasubiculum and the cells in the entorhinal cortex that give rise to the perforant pathway have been studied in the rat at the light microscopical level. Projections from the presubiculum and the parasubiculum were labeled anterogradely, and, in the same animal, cells in the entorhinal cortex that project to the hippocampal formation were labeled by retrograde tracing and subsequent intracellular filling with Lucifer Yellow. The distribution and the number of appositions between the afferent fibers and hippocampal projection neurons in the various layers of the entorhinal cortex were analyzed. The results show that layers I–IV of the entorhinal cortex contain neurons that give rise to projections to the hippocampal formation. The morphology of these projection neurons is highly variable and afferents from the presubiculum and the parasubiculum do not show a preference for any specific morphological cell type. Both inputs preferentially innervate the dendrites of their target cells. However, presubicular and parasubicular projections differ with respect to the layer of entorhinal cortex they project to. The number of appositions of presubicular afferents with cells that have their cell bodies in layer III of the entorhinal cortex is 2–3 times higher than with cells in layer II. In contrast, afferents from the parasubiculum form at least 2–3 times as many synapses on the dendrites of cells located in layer II than on neurons that have their cell bodies in layer III. Cells in layers I and IV of the entorhinal cortex receive weak inputs from the presubiculum and parasubiculum. Not only is the presubiculum different from the parasubiculum with respect to the distribution of projections to the entorhinal cortex, they also differ in their afferent and efferent connections. In turn, cells in layer II of the entorhinal cortex differ in their electrophysiological characteristics from those in layer III. Moreover, layer II neurons give rise to the projections to the dentate gyrus and field CA3/CA2 of the hippocampus proper, and cells in layer III project to field CA1 and the subiculum. Therefore, we propose that the interactions of the entorhinal-hippocampal network with the presubiculum are different from those with the parasubiculum.
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  • 136
    ISSN: 1432-1106
    Keywords: Calcium ions ; Neurons ; Acid-base changes ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of changes in intra- and extracellular pH (pHi and pHe, respectively) on the cytosolic, free calcium concentration ([Ca2+]i) of neocortical neurons was studied by microspectrofluorometric techniques and the fluorophore fura-2. When, at constant pHe, pHi was lowered with the NH4Cl prepulse technique, or by a transient increase in CO2 tension, [Ca2+]i invariably increased, the magnitude of the rise being proportional to ΔpHi. Since similar results were obtained in Ca2+-free solutions, the results suggest that the rise in [Ca2+]i was due to calcium release from intracellular stores. The initial alkaline transient during NH4Cl exposure was associated with a rise in [Ca2+]i. However, this rise seemed to reflect influx of Ca2+ from the external solution. Thus, in Ca2+-free solution NH4Cl exposure led to a decrease in [Ca2+]i. This result and others suggest that, at constant pHe, intracellular alkalosis reduces [Ca2+]i, probably by enhancing sequestration of calcium. When cells were exposed to a CO2 transient at reduced pHe, Ca2+ rose initially but then fell, often below basal values. Similar results were obtained when extracellular HCO 3 - concentration was reduced at constant CO2 tension. Unexpectedly, such results were obtained only in Ca2+-containing solutions. In Ca2+-free solutions, acidosis always raised [Ca2+]i. It is suggested that a lowering of pHe stimulates extrusion of Ca2+ by ATP-driven Ca2+/2H+ antiport.
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  • 137
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    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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  • 138
    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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  • 139
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    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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  • 140
    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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  • 141
    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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  • 142
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    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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  • 143
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    Experimental brain research 100 (1994), S. 85-92 
    ISSN: 1432-1106
    Keywords: Object recognition ; Configural discrimination ; Memory ; Fornix ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of fornix lesions were examined in an object recognition memory test based on spontaneous exploration. In the standard condition an object (A) was presented in the sample phase and then presented again in the test phase alongside a new object (B). Both fornix-transected (Fx) and control (Co) rats spent more time exploring the new object than the familiar object after retention delays of 1 min and 15 min. In two configural conditions designed to test sensitivity to reconfigured stimuli, the original sample (A) was now either re-presented alongside its rearranged version (∀), or the re-arranged version itself (∀) was presented with a new object (B). In the first configural condition, both the Co and Fx rats spent more time exploring the reconfigured sample (∀) than the original version of the sample (A) following a delay of 1 min, but not 15 min. In the second configural condition, both Co and Fx rats spent more time exploring the new object (B) than the reconfigured version of the sample (∀) following a delay of 15 min but not 1 min. These present results do not support Sutherland and Rudy's hypothesis on hippocampal function; however, they demonstrate that memory of objects as well as memory of reconfigured objects could easily be examined in a test based on spontaneous exploratory behaviour.
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  • 144
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    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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  • 145
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    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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  • 146
    ISSN: 1432-1912
    Keywords: Nitric oxide ; NG-nitro-L-arginine methyl ester ; Kidney ; Heart ; Hypertension ; Renal haemodynamics ; Renin-angiotensin system ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-l-arginine methyl ester (l-NAME). Chronic treatment with l-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 ± 16 mmHg) as compared to controls (155+4 mmHg). Animals receiving simultaneously l-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56+0.73 ml·kg−1·min−1) and renal plasma flow (RPF: 6.93±1.70ml·kg−1·min−1) as compared to control (GFR: 7.29±0.69, RPF: 21.36±2.33ml·kg−1·min−1). Addition of ramipril prevented l-NAME-induced reduction in GFR and renal plasma flow. l-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with l-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischaemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased. Coadministration of ramipril reversed these effects. l-NAME treatment reduced the cyclic GMP content in urine and renal arteries, and was not changed by additional ramipril-treatment. In the kidney hyalinosis of arterioles and of glomerular capillaries, as well as mesangial expansion and tubular atrophies seen after long-term inhibition of NO synthase were reduced by coadministration of ramipril. In conclusion, long-term ACE inhibition by ramipril prevented l-NAME-induced hypertension and cardiac hypertrophy, and attenuated functional and morphological changes in the kidneys. In addition, cardiac-dynamic and -metabolic deterioration induced by L-NAME was normalised by co-treatment with ramipril.
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  • 147
    ISSN: 1432-1920
    Keywords: Pituitary adenoma ; MRI ; Immunohistochemistry ; Pituitary hormones
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Our aim was to elucidate the factors which determine the MRI signal intensities of pituitary adenomas. We examined 51 patients with surgically-confirmed pituitary adenomas. Using a spin-echo pulse sequence (SE 500/15), coronal and sagittal images (3 mm slices) were obtained. Signal intensities on T1-weighted images were measured in the parenchyma of the adenoma and in normal grey matter. The relative intensity of the adenoma was assessed by calculating the ratio of its signal intensity to that of the normal grey matter of the same patient. Parafin-embedded sections were used for haematoxylin and eosin staining. The number of cells in a prescribed area was counted, and the mean of five such counts was taken as the cell density. Immunohistochemically stained sections using antibodies for various pituitary hormones were similarly examined; the ratio of the total number of hormone-positive cells to the overall total number of adenoma cells was calculated. Four independent variables were used in the analysis: the age of the patient, the maximum diameter of the adenoma, the cell density and the proportion of hormone-positive cells in the adenoma and, with the signal intensity ratio as the dependent variable, a multiple regression analysis was performed. This revealed that the the greatest influence upon the signal intensities on T1-weighted images was the proportion of hormone positive cells.
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  • 148
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    Der Pathologe 15 (1994), S. 181-186 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Angiosarkom ; Nebenniere ; Immunhistochemie ; Intermediärfilamente ; Zytokeratine ; CD 31 ; Key words Angiosarcoma ; Adrenal gland ; Immunohistochemistry ; Intermediate filaments ; Cytokeratins ; CD 31
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Cytological, biopsy and autopsy findings in a patient suffering from massively metastasizing adrenal angiosarcoma are reported. Histogenetic typing of the tumour initially manifestating itself by osseous and liver metastases was problematic with regard to its partially epithelioid structure and its positivity upon cytokeratin immunostaining. Of relevance for the correct typing was the finding that the tumour cells in addition exhibited positivity for vascular markers. This case confirms literature data according to which cytokeratin expression not infrequently may be encountered in endothelial neoplasms and which by no means should lead to exclude such a tentative diagnosis.
    Notes: Zusammenfassung Berichtet wird über zytologische, bioptische und autoptische Befunde bei einem Patienten mit fortgeschritten metastasiertem adrenalen Angiosarkom. Die korrekte histogenetische Klassifikation der sich zunächst durch ossäre und Leberabsiedlungen manifestierenden teilweise epitheloiden Neoplasie war konventionell-morphologisch und wegen des immunhistologisch positiven Zytokeratin-Nachweises problematisch. Bedeutung für die Diagnosesicherung hatte die zusätzlich nachgewiesene Positivität der Tumorzellen für vaskuläre Marker. Der beschriebene Fall bestätigt Literaturbefunde, nach denen eine Zytokeratin-Expression unter Angiosarkomen nicht selten angetroffen wird und keinesfalls zum Ausschluß einer entsprechenden Verdachtsdiagnose führen darf.
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  • 149
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Autoklavieren ; Mikrowelle ; Immunhistochemie ; Antigen-Demaskierung ; Key words Wet autoclaving ; Microwave pretreatment ; Immunohistochemistry ; Antigen retrieval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Wet autoclaving is a simple, reliable and time-effective method for antigen retrieval in routinely processed archival material. Both routine diagnostic (e. g., oestrogen and progesterone receptors, cytoskeletal proteins) and research antibodies (e. g. various p53 antibodies, mdm-2, bcl-2, MIB-1) are reported to demonstrate its application. Wet autoclaving may allow successful application of antibodies in paraffin-embedded tissues designed for use on frozen sections. The technique has the poten-tial to reliably handle up to 200 sections at a time, without evidence of any significant damage to the sections or nuclear morphology.
    Notes: Zusammenfassung Mit der Technik des feuchten Autoklavierens wird eine einfache, verläßliche und zeitsparende Methode zur Antigen-Demaskierung an Formalin-fixiertem und Paraffin-eingebettetem Gewebe vorgestellt. Anhand einer Reihe von Antikörpern (Östrogen- und Progesteronrezeptoren, Zytoskelettproteine, verschiedene p53-Antikörper, mdm-2, bcl-2, MIB-1 u. a.) verwendeter Antikörper werden die Vorteile dieser Methode beschrieben. Das feuchte Autoklavieren ermöglicht bei einigen sonst nur am Gefrierschnitt einsetzbaren Antikörpern auch deren Anwendung am Paraffinschnitt. Für den Routinepathologen ist die leichte Handhabung sowie die hohe Reproduzierbarkeit von Vorteil.
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  • 150
    ISSN: 1432-1963
    Keywords: Schlüsselwörter bcl-2 ; Osteosarkom ; Apoptose ; programmierter Zelltod ; Immunhistologie ; Proliferation ; Key words bcl-2 ; Osteosarcoma ; Apoptosis ; programmed cell death ; Immunohistochemistry ; Proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The relationsship between the growth of tumors and the expression of the protooncogen Bcl-2 could be shown in epithelial tumors. A bcl-2 expression leads to a prolonged cell survival due to an inhibition of apoptosis. The potential meaning of bcl-2 expression in mesenchymal tumors remains still unknown. The fact, that the heterogenous group of osteosarkoma is not sufficiently characterized at present, suggested to investigate the bcl-2 expression in osteosarcoma. Thus, immunohistochemistry was used to analyze 47 specimens of different osteosarcomas of 36 patients. Sixteen cases (46 %) showed a strong expression of bcl-2 and 13 cases (35 %) were moderately positiv for bcl-2. Seven cases (19 %) were negative for bcl-2. The heterogenous, negative up to strong expression of bcl-2 yield clues, that the Bcl-2 controlled regulation of programmed cell death could be an important factor of cellular kinetics. Additionally the cellular proliferationrate was determined with the monoklonal antibody MIB 1, directed against the Ki-67 epitop. The data of bcl-2 expression and cellular proliferationrate lead to a classification correlating with the histological classification. To verify the importance of apoptosis in the genesis of mesenchymal tumors and whether Bcl-2 may play an important role as a predictive factor for the prognosis of osteosarcoma, further investigations will be needed.
    Notes: Zusammenfassung Bei zahlreichen epithelialen Geweben konnte ein Zusammenhang zwischen Tumorwachstum und der Expression des Protoonkogens Bcl-2 nachgewiesen werden. Eine bcl-2-Expression ist verbunden mit verlängertem Zellüberleben infolge einer Apoptoseinhibition. Hingegen ist über die bcl-2-Expression und deren mögliche Bedeutung in mesenchymalen Tumoren wenig bekannt. Da die heterogene Gruppe der Osteosarkome mit den derzeitigen methodischen Mitteln nicht hinreichend charakterisierbar ist, wurde die bcl-2-Expression untersucht. Immunhistologisch wurden 47 Osteosarkompräparate von 36 Patienten unterschiedlicher Subtypen analysiert. Von den 36 Fällen zeigten in der Biopsie 16 Fälle (46 %) eine stark positive und 13 Fälle (35 %) eine mittelgradig positive bcl-2 Expression. Sieben Fälle (19 %) waren bcl-2-negativ. Die heterogene, fehlende bis starke bcl-2-Expression deutet darauf hin, daß in Osteosarkomen die Bcl-2-gesteuerte Regulation des programmierten Zelltodes einen Faktor in der zellulären Wachstumskinetik darstellt. Zusätzlich wurde die Proliferationsrate, anhand des gegen das Ki-67-Antigen gerichteten monoklonalen Antikörper MIB-1 bestimmt. Aus den Daten zur bcl-2-Expression und Proliferationsrate ergibt sich eine Einteilung, die eine Übereinstimmung mit der histologischen Klassifikation aufweist. Welche Bedeutung die Apoptose in der Genese mesenchymaler Tumoren hat und ob die bcl-2-Expression einen prädiktiven Wert für die Prognose von Osteosarkomen besitzt, bedarf weiterer Untersuchungen.
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  • 151
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    Der Pathologe 15 (1994), S. 358-360 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Tonsillentumor ; Primär extrakranielles Meningeom ; Atypisches Meningeom ; Immunhistologie ; Key words Tumour of the palatine tonsil ; Primary extracranial meningioma ; Atypical meningioma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To our knowledge this is the first reported case of a primary extracranial meningioma located in the palatine tonsil. Immunohistochemical investigation of the tumour showed coexpression of vimentin and neuron-specific enolase (NSE). No staining was found with antibodies against cytokeratins KL 1, 13/10, 8 and 18, epithelial membrane antigen EMA and melanoma protein (HMB-45). It seems justifiable to classify this tumour as an atypical meningioma because of the local increased mitotic activity.
    Notes: Zusammenfassung Dieses ist nach unseren Kenntnissen der 1. Fallbericht eines primär extrakraniellen, in der Tonsille lokalisierten Meningeoms. Immunhistologisch wies der Tumor eine Koexpression von Vimentin und neuronspezifischer Enolase (NSE) und eine negative Reaktion mit Antikörpern gegen die Zytokeratine KL 1, 13/10, 8, 18, das epitheliale Membranantigen EMA und Melanom Protein (HMB 45) auf. Aufgrund der lokal gesteigerten Mitoserate scheint es gerechtfertigt, den vorliegenden Tumor als atypisches Meningeom zu klassifizieren.
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  • 152
    ISSN: 1432-198X
    Keywords: Glomerular filtration rate ; Technetium-DTPA ; Hyperfiltration ; Uninephrectomy ; High-protein diet ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been suggested that a prolonged course of hyperfiltration could lead to progressive deterioration of renal function. In order to test this hypothesis, the following protocol was applied to 60 male Wistar rats. At 12 weeks of life, the rats were submitted to a surgical procedure: sham operation (25 rats), unilateral nephrectomy (25 rats) or 3/4 nephrectomy (10 rats). The three groups were again divided into two subgroups: one with high-protein intake (36%) and one with a low-protein intake (12%). In order to avoid any additional traumatic procedure which could shorten the animal's life, the glomerular filtration rate (GFR) was measured without blood sampling, using a previously validated technique based on an image recorded by a gamma camera between the 9th and the 10th min after intravenous injection of99m technetium diethylenetriaminepentaacetate (DTPA). The sum of both kidneys and bladder activity was expressed as a percentage of the injected dose. The test was performed before surgery and every month thereafter. Six weeks after surgery, the highest filtration rate was found in the rats with “two kidneys/high-protein diet”, followed by the “two kidneys/low-protein diet”, the “one kidney/high-protein diet”, the “one kidney/low-protein diet” and the “1/2 kidney”. The overall GFR in the one kidney/high-protein diet rat and in the 1/2 kidney rat was respectively 80% and 55% of the pre-operative values. Until 109 weeks of age, the survival rate was comparable in the five groups of rats. At 109 weeks of age, non-significant changes in renal function were observed, the follow-up slopes of the different subgroups being more or less parallel. At that age, the lesions of glomerular sclerosis were focal and discrete, without significant differences in the five groups.
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  • 153
    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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  • 154
    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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  • 155
    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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  • 156
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    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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  • 157
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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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  • 158
    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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  • 159
    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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  • 160
    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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  • 161
    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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  • 162
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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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  • 163
    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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  • 164
    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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  • 165
    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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  • 166
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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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  • 167
    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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  • 168
    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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  • 169
    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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  • 170
    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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  • 171
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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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  • 172
    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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  • 173
    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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  • 174
    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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  • 175
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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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  • 176
    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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  • 177
    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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  • 178
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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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  • 179
    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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  • 180
    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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  • 181
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    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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  • 182
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    Experimental brain research 101 (1994), S. 73-85 
    ISSN: 1432-1106
    Keywords: Substantia nigra ; Striatum ; Transplant Dopamine ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The ability of mature dopaminergic neurons derived from ventral mesencephalon to re-initiate growth after making contact with a non-innervated target was studied using the intra-ocular grafting model. Foetal ventral mesencephalic tissue or brain stem including the locus coeruleus area was grafted to the anterior chamber of the eye. Two weeks, 6 weeks or 1 year after the first implantation, foetal striatal tissue was placed in contact with the nigral graft or grafted alone. The size of the transplants was measured through the cornea. The final size of the striatal grafts was significantly larger when placed alone than when co-grafted with 1-year-old or 6-week-old dopaminergic grafts. Striatum grafted together with 2-week-old nigra was larger than when grafted adjacent to mature substantia nigra, but not significantly so. Nerve fibre outgrowth into the iris from the nigral transplants did not increase after maturation, but the re-innervated area of the host iris progressively increased around the locus coeruleus grafts. Ingrowth of tyrosine hydroxylase (TH) immunoreactive nerve fibres into the striatal grafts was studied 6 weeks after the second implantation. TH immunohistochemistry revealed innervation of the striatal piece in all cases, except for the group where striatum alone was grafted. With the short survival time for cografts of 6 weeks, TH-positive nerve fibres innervated a larger volume, had a patchy appearance and the density was higher in striatum grafted to 2 week-old nigral transplants than that seen in striatal transplants grafted to mature nigral grafts. The patchy pattern of TH-immunoreactive nerve terminals was also seen in striatum co-grafted with 6-week-old or 1-year-old nigral transplants. No difference in striatal innervation volume was detected between those latter two groups. When striatum was implanted adjacent to mature ventral mesencephalon and grown together for 6 months — the longer survival time — the same dense TH-positive innervation as seen in striatum co-grafted with immature nigral tissue at the shorter survival time was found. Additionally, the nigral part of the co-grafts showed increased TH-immunoreactive nerve fibre density. In conclusion, dopaminergic neurites from mature ventral mesencephalic transplants can re-initiate growth if placed in contact with non-innervated striatal tissue. The nigral grafts do not progressively re-innervate the host iris, while locus coeruleus grafts do. The intra-ocular grafting model can be used to study the in vivo effects of trophic factors on mature dopaminergc neurons.
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  • 183
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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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  • 184
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    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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  • 185
    ISSN: 1432-1106
    Keywords: Amoeboid microglia Major histocompatibility complex Type 3 complement receptor ; Endotoxin ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In rats given two single intraperitoneal injections of lipopolysaccharide (LPS) at 1 and 4 days of age and killed at 7 days of age, 11.5–12% of amoeboid microglial cells (AMC) in the supraventricular corpus callosum were induced to express major histocompatibility complex (MHC) class II antigen, as detected with monoclonal antibody OX-6. The MHC class II antigen induced was colocalized with MHC class I antigen and type 3 complement receptors on the same cells. The expression of MHC class II antigen on the plasma membrane of AMC was confirmed in immunoelectron microscopy. Although OX-6-positive AMC often assumed a perivascular position, the majority of them, however, were far removed from the blood vessels. The cytoplasmic processes of the perivascular OX-6-positive AMC appeared to rest directly on the vascular lamina, and in some section profiles they were in contact with a large surface area of the outer wall of small blood vessels. It is concluded from this study that although MHC class II antigen is not constitutively present on AMC, it is, however, inducible under stimulation with LPS. It is, therefore, suggested that the OX-6-positive AMC, especially the perivascular AMC, may have the potentiality to function as antigen-presenting cells in the developing brain when challenged by LPS.
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  • 186
    ISSN: 1432-1106
    Keywords: Acidosis ; Seizures ; Brain slices ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lowering [Mg2+]o induces epileptiform bursting in hippocampus and entorhinal cortex (EC), presumably by activation of N-methyl-d-aspartate (NMDA) receptors. Since increasing [H+]o has been shown to reduce NMDA receptor activation, we hypothesized that this could contribute to anticonvulsant actions of acidic pH. To test this, we studied the effects of raising extracellular PCO2 (20.6%, pH = 6.7) or lowering extracellular pH (6.7 or 6.2) on low-Mg2+-induced epileptiform discharges. Lowering the pH to 6.7 by either means increased the interval between seizure-like events (SLEs), decreased the maximal amplitude of SLEs, and, if the site of seizure generation was at a distance from the recording site, acidification slowed the rate of seizure propagation. In contrast, the duration of SLEs was unaffected by acidic pH or high PCO2. Raising PCO2 or lowering pH to 6.7 also blocked early (8–10 min) but not late (〉 20 min) phases of status-like discharges. All effects of the extracellular pH changes were fully reversible. Further lowering of extracellular pH to 6.2 completely and reversibly blocked both SLEs and status-like discharges. Our data show that the effects of high PCO2 and low pH on seizures in the EC in vitro may be dose-dependent and consistent with induction by proton blockade of NMDA receptors. Thus, blockade of NMDA currents by protons may be an important component of the anticonvulsant action of extracellular acidosis. The results also suggest that acidosis may be a desirable property for new antiepileptic treatments.
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  • 187
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    Experimental brain research 101 (1994), S. 59-72 
    ISSN: 1432-1106
    Keywords: Spinal cord ; Synaptic transmission ; GABAB receptors ; Baclofen agonists and antagonists ; Rat ; Cat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre-and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35 348, 36 742, 46 381, 52 432, 54 626 and 55 845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre-and postsynaptic inhibitory effects of 3-aminopropyl-methyl-osphinic acid (CGP 35 024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35 024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre-and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55 845 and 46 381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.
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  • 188
    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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  • 189
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    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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  • 190
    ISSN: 1432-0738
    Keywords: Key words Tobacco-specific nitrosamine ; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone ; [4-(Methylnitrosamino)-1-(3-pyridyl)but-1-yl]- β-O-d-glucosiduronic acid ; Rat ; Urine ; Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Besides 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O-d-glucosiduronic acid (NNAL-Glu) is another important metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which has been detected in the urine of tobacco users and non-smokers heavily exposed to sidestream cigarette smoke. In order to evaluate the toxicological significance of NNAL-Glu formation and excretion, the metabolism of [5-3H]-NNAL-Glu was studied in rats. Five male F344 rats were administered 3.7 mg/kg [5-3H]-NNAL-Glu by i.v. injection and the metabolites in urine analysed by HPLC. More than 90% of the radioactivity was excreted in urine within the first 24 h. Unchanged NNAL-Glu accounted for 81.2±3.1% of the total radioactivity; the remaining part of the dose appears to be deconjugated resulting in the urinary excretion of NNAL (3.6±1.7%) and its α-hydroxylation (11.5±2.2%) and N-oxidation (3.6±1.6%) products. The presence of α-hydroxylation products of NNAL-Glu in urine suggests that this NNK metabolite may be activated in vivo to carcinogenic intermediates.
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  • 191
    ISSN: 1432-0738
    Keywords: Key words Cell proliferation ; Pancreas ; 5-Bromo-2′-deoxyuridine (BrdU) ; Immunohistochemistry ; Hormones ; Insulin ; Glucagon ; Somatostatin ; Phenobarbitone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A previous study demonstrated that administration of phenobarbitone to male AP Wistar rats for up to 7 days caused alterations in labelling indices (LIs) in several different tissues (including a reduction of the endocrine pancreas population LI) as determined by immunohistochemical visualisation of 5-bromo-2′-deoxyuridine (BrdU) incorporation into S-phase nuclei. The primary objective of this study was to determine whether treatment with phenobarbitone influenced the replicative states of specific cohorts of the islet (of Langerhans) cell population or generated a uniform depression of LI. Quantitation of the LIs of individual islet cell cohorts was achieved by utilisation of a dual immunohistochemical staining method for BrdU and islet hormones (insulin, glucagon and somatostatin) using a sequential peroxidase anti-peroxidase (PAP)/alkaline phosphatase anti-alkaline phosphatase (APAAP) method employing diaminobenzidine and New Fuchsin chromogens, respectively. We observed reductions, increases and no change in LIs of insulin-, glucagon- and somatostatin-positive cells, respectively. We conclude that the decreased LI of the insulin-positive cohort was not countered entirely by the LI increase in the glucagon-positive cohort due to the larger size of the former. Furthermore, the effects of phenobarbitone treatment are not manifested generally in the islet cell population but in the insulin- and glucagon-positive cohorts only. The causation of these effects is unknown but is likely to be due to enhanced carbohydrate and hormone metabolism. We believe that the visualisation and quantitation of replicating cells in specific hormone-positive cohorts of the islet cell population provide opportunities for understanding the influence of xenobiotics and disease processes on pancreatic function.
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  • 192
    ISSN: 1432-0738
    Keywords: Key words Nasal cavity ; Immunohistochemistry ; Glutathione S-transferases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Many xenobiotics induce lesions within the nasal cavity of experimental animals which are site specific. This site selectivity may be due to regional deposition within the nasal cavity and/or the localisation of biotransformation enzymes. We have developed methodology which allows immunohistochemical localisation of xenobiotic biotransformation enzymes in transverse sections of the rat nasal cavity identical to those normally taken for pathological examination. We report the application of this methodology to six isoenzymes of the glutathione S-transferases (GSTs). All six isoenzymes were predominantly located within olfactory epithelium covering the ethmoturbinates (levels III and IV) and extending forwards into the dorsal meatus (level II). Squamous and transitional epithelia showed little or no staining while respiratory epithelium was weakly stained. Within the respiratory epithelium only the ciliated columnar cells and, to a lesser extent, some of the seromucous glands contained GSTs. Within olfactory epithelium the sustentacular cells, basal cells and subepithelial glands all stained positive for GSTs. The different cell types of olfactory epithelium preferentially express different GST isoenzymes: 1-1 and 2-2 were predominantly located in the subepithelial glands; 3-3, 4-4 and 8-8 in sustentacular and basal cells; 7-7 in basal cells.
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  • 193
    ISSN: 1432-1750
    Keywords: Rat ; DNA ; mRNA ; Collagen ; Fibronectin ; c-myc
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Continuous exposure of rats to ozone has been shown to result in lung epithelial damage, inflammation, and subsequent increases in collagen content. The main goal of this study was to identify the earliest time point of altered extracellular matrix protein gene expression by utilizing Northern blot analyses of rat lungs continuously exposed to 1.0 ppm ozone for 14 days. An early increase of steady-state fibronectin mRNA levels was observed at 2 days of exposure, prior to the time point of increased type I collagen mRNA, which was seen at 4 days. This increased level of type I collagen mRNA preceded measurable changes in total lung collagen content, observed at 7 days. In addition, peak levels of the growth-related proto-oncogene c-myc mRNA could be correlated with maximal increases of lung DNA content, although the initial increase in c-myc mRNA preceded measurable changes of total lung DNA. The use of specific cDNA probes for measuring altered gene expression can be useful for defining the early cellular and molecular events in ozone-induced lung injury.
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  • 194
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    Archives of gynecology and obstetrics 255 (1994), S. 181-187 
    ISSN: 1432-0711
    Keywords: Endometriosis ; Estrogen- and progesterone receptors ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 30 formalin-fixed and paraffin embedded and 20 fresh frozen samples of endometriotic tissue were analysed immunohistochemically for the concentration of estrogen and progesterone receptors. In the formalin-fixed and paraffin embedded group only 37% of the samples were estrogen receptor positive whereas 63% were receptor negative. In contrast, we found that 67% of the samples had a positive progesterone receptor status. In the fresh frozen group 60% of endometriotic tissues were estrogen receptor positive and 75% of the tissues had a positive progesterone receptor status. We could not find any correlation between the site or severity of the endometriosis or the hormonal receptor status. We were able to demonstrate that the immunohistochemical detection of hormonal receptors in endometriotic tissues is possible and that better results were obtained if fresh frozen rather than formalin-fixed and paraffin embedded tissues were analyzed.
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  • 195
    ISSN: 1432-0711
    Keywords: Filaggrin ; Immunohistochemistry ; Squamous differentiation ; Uterine Cervix
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epithelial distribution of filaggrin, a histidine-rich protein related to squamous terminal differentiation, was investigated in 87 cervical biopsies using an avidin-biotin-peroxidase technique with a monoclonal anti-human filaggrin antibody (AKH1). Normal squamous cervical epithelium exhibited a positive homogeneous immunoperoxidase stain in the upper parabasal, intermediate and superficial cell layers. Similar findings were obtained in cervical condylomas, although full-thickness staining was observed in 35.7% of the cases (P〈0.001). Filaggrin expression in CIN was inversely related to the severity of the lesion (P〈0.001). An irregular staining pattern was present in most high-grade CIN. Filaggrin expression was closely connected to the degree of tumour differentiation (P〈0.05) in squamous cell carcinomas of the cervix. Abnormal filaggrin stainings identified a premalignant/malignant cervical squamous lesion with a positive predictive value of 92.3%. Non-squamous epithelia showed lack of filaggrin expression. Filaggrin may therefore be considered a marker of squamous differentiation in both the normal and pathological human uterine cervix.
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  • 196
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    Journal of cancer research and clinical oncology 120 (1994), S. 672-677 
    ISSN: 1432-1335
    Keywords: Ovary ; Undifferentiated carcinoma ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidinbiotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), α-fetoprotein (AFP), α-l-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2,bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining forbcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further celarly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.
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  • 197
    ISSN: 1432-2161
    Keywords: Arthritis ; Rat ; Knee ; MRI ; X-radiography ; histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract High-resolution magnetic resonance imaging (MRI) has been used to visualise the changes that occur in both soft tissue and bone during antigen-induced, monoarticular arthritis (AIMA) of the rat knee. Extensive optimisation studies were performed in order to minimise the time of the experiments and to maximise both the signal-to-noise ratio and the contrast in the MR images. The study was cross-sectional rather than longitudinal and at each of the 13 time points studied during the progression of the disease, corresponding X-radiographs and histological sections were obtained. Interpretation of the spin echo MR images was aided by the use of chemical shift-selective imaging, magnetisation transfer contrast and relaxation time experiments, as well as by correlation with the histology and X-radiography data. The MR images clearly show invasion of the synovium by an inflammatory pannus which spreads over the articular cartilage and invades the bone, leading to erosion and later remodelling. Two distinct types of bony erosion were observed: focal erosions, especially at the margins of the joint, and subchondral erosions. It is concluded that MRI provides a sensitive, non-invasive method for investigating both early-stage inflammatory changes and late-stage bony changes in the knee joints of the arthritic rat.
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  • 198
    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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  • 199
    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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  • 200
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    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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