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  • hippocampus  (40)
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  • 1
    ISSN: 1435-1463
    Keywords: Electroconvulsive shock ; 5-HT1A receptor ; 5-HT1b receptor ; hippocampus ; microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In vivo microdialysis was used to determine the effects of chronic electroconvulsive shock (ECS), given daily for 10 days, on basal 5-HT levels in rat frontal cortex and hippocampus and on the effect of systemic administration of the 5-HT-la receptor agonist, 8-OH-DPAT (0.2 mg/kg), to reduce 5-HT levels in these areas by activation of somatodendritic autoreceptors. Neither basal 5-HT levels nor the effects of 8-OH-DPAT on 5-HT levels were altered after chronic ECS. The effect of systemic administration of the 5-HT1A and 5-HT1B antagonist, (±)-pindolol (10mg/kg), to increase 5-HT levels in hippocampus, was also not affected by chronic ECS.
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  • 2
    ISSN: 1435-1463
    Keywords: [3H]paroxetine ; hippocampus ; schizophrenia ; neuroleptic drugs ; suicide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary [3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd=0.50 ± 0.04 vs. 0.24 ± 0.02nM; mean ± S.E.M. p 〈 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd=0.50 ± 0.07 vs. 0.50 ± 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.
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  • 3
    ISSN: 1435-1463
    Keywords: Learning ; memory ; NMDA-receptor density ; cerebral cortex ; hippocampus ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hippocampal NMDA-receptor is predominantly involved to establish long-term potentation (LTP) which is assumed to underlie fundamental molecular mechanisms of learning and memory. In the present study, NMDA-receptor density was investigated in parietotempral cerebral cortex and in hippocampus of commonly bred naive adult male Wistar rats which had performed well or poorly in the passive avoidance paradigm. NMDA-receptor binding was determined in saturation experiments using (3H) MK-801 as a ligand and data for K d and Bmax were calculated from Scatchard plots. In general, higher NMDA receptor density was found in the hippocampus as compared to parietotemporal cerebral cortex. This regional difference became particularly obvious in good performers but was abolished in poor performers. In the hippocampus, a significantly higher NMDA-receptor density could be found in rats which had performed well in the passive avoidance task as compared to poor performers. In contrast, no such differences could be found in parietotemporal cerebral cortex. The data may indicate that the reduction in hippocampal NMDA-receptor density is of functional importance, for cognitive abilities in both physiological and pathophysiological conditions.
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  • 4
    ISSN: 1435-1463
    Keywords: Keywords: Epilepsy ; hippocampus ; dentate granule cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Recurrent, feedback excitation by sprouted mossy fibers may contribute to the hyperexcitability observed in human temporal lobe epilepsy. Observations in rodent models of epilepsy mimic the findings in human tissue and reveal that dentate granule cells sprout axons which innervate fibers in their own dendritic layer. However, recent evidence in rodents suggest that these sprouted fibers may form connections which cause inhibition of dentate granule cells, not excitation. Thus, the net effect of sprouting in human epileptic tissue may not only be recurrent excitation. We analyzed paired pulse depression in dentate slices from 9 patients with temporal lobe epilepsy and found evidence for strong feedback inhibition. We also noted failure of high frequency stimulation induced inhibition in our human specimens. These data challenge the concept that human epileptic dentate granule cells are excited by recurrent mossy fiber sprouting.
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  • 5
    ISSN: 1435-1463
    Keywords: Keywords: Pilocarpine ; kainate ; seizures ; thyrotropin-releasing hormone ; mRNA ; hippocampus ; rat.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The expression of mRNA coding for prepro-thyrotropin releasing hormone (preproTRH) was estimated in the rat brain in two animal models of limbic seizures, evoked by systemic administration of pilocarpine (400 mg/kg ip) or kainate (12 mg/kg ip). As shown by an in situ hybridization study, after 24 h both pilocarpine- and kainate-induced seizures profoundly increased the preproTRH mRNA level in the dentate gyrus. After 72 h, the preproTRH mRNA level was back to control values. Kainate-treated rats showed an elevated level of TRH in the hippocampus, septum, frontal and occipital cortex after 24 and 72 h, whereas in the striatum and amygdala the TRH level was raised after 72 h only. In the hypothalamus, TRH levels was lowered after 3 and 24 h, and returned to the control after 72 h. Pilocarpine-induced seizures also elevated the TRH level after 72 h in the majority of the above structures, except for the hypothalamus and amygdala where no changes were found at any time point. A radioreceptor assay showed that kainate decreased the Bmax value of TRH receptors in the striatum and hippocampus after 3 and 24 h, respectively, and had no effect on the Kd values. In contrast, pilocarpine-induced seizures lowered the Bmax of TRH receptors in the striatum, hippocampus and piriform cortex after 72 h only, and decreased Kd values in the striatum, amygdala and frontal cortex. These data showed that pilocarpine- and kainate-induced seizures enhanced likewise preproTRH mRNA in the dentate gyrus; on the other hand, they differed with respect to time- and structure-related changes in TRH tissue levels and TRH receptors. These differences may have functional significance in TRH-dependent control mechanism of the seizure activity in these two models of limbic epilepsy.
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  • 6
    ISSN: 1435-1463
    Keywords: Adenosine ; hippocampus ; behaviour ; exploratory behaviour
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possible effects of Adenosine (AD), locally applied into the ventral Hippocampus (HPCv) on the expression of general motor activity and some stereotyped behaviours were studied in adult male rats. Locomotion display was recorded in a hole-board equiped with automatic infrared animal activity detectors. Stereotyped behaviours were measured by direct inspection by two observers. Animals were implanted with microinjection cannulae into the HPCv and 72 h later they were injected with saline, or increasing doses of AD. In one experiment rats were microinjected once with saline or Adenosine and general motor activity and exploration were examined. In other experiment, rats were injected into the HPCv twice with saline, the AD-receptors antagonist 1,3-dipropil-methyl-xanthine (DMX) or AD and only stereotyped behaviours were examined. Results of Experiment 1 showed that the 40 nMol dose of AD was significantly effective to inhibit by about 30% several motor activities such as vertical, horizontal and ambulatory behaviours. Results of Experiment 2, showed that grooming was not modified by AD but the dose of 10 nMol increased the time of immobility by about 3 times over controls. DMX was able to block completely the AD effects on immobility. The present results suggest that in the rat AD might modulate the hippocampal-mediated expression of some motor and stereotyped behaviours induced by unknown environments.
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  • 7
    ISSN: 1435-1463
    Keywords: Microdialysis ; serotonin ; 5-HT1a receptor ; buspirone ; dorsal raphé ; hippocampus ; TTX
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1μM and 10μM) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10μM), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged. Systemic injections with the 5-HT1a agonist, buspirone (1.0–5.0mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in the dorsal raphé and in the hippocampus. The decreases in raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.OmM (−) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (−) pindolol alone (0.01–1.0mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100nM), or produced a small increase (1.0mM) in raphé 5-HT, without changing hippocampal 5-HT. These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT1a receptors control somatodendritic and hippocampal 5-HT release.
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  • 8
    ISSN: 1435-1463
    Keywords: Glucocorticoid receptor mRNA ; hippocampus ; desipramine (DMI) ; (+) and (−)-oxaprotiline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Male Sprague-Dawley rats were treated for 7 days with the norepinephrine (NE) uptake inhibitors desipramine (DMI) or (+)-oxaprotiline or the inactive (−)-enantiomer of oxaprotiline. DMI, as previously reported, significantly increased hippocampal glucocorticoid receptor (GR) mRNA while the equipotent NE uptake inhibitor (+)-oxaprotiline like the inactive (−)-oxaprotiline did not alter hippocampal levels of GR mRNA. The results indicate that an increase in the synaptic availability of NE as a consequence of uptake inhibition is not responsible for the action of DMI on GR gene expression.
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  • 9
    ISSN: 1435-1463
    Keywords: MK801 ; phencyclidine ; NMDA receptor ; hippocampus ; psychosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have previously shown that a single dose of PCP produces a dose-related increase in NMDA-sensitive3H-glutamate binding in CA1 of hippocampus 24 hours later, and some regional changes in kainate binding. Here we report that dizocilpine (MK 801) (O.1 mg/kg and 1 mg/kg), a selective agonist at the PCP receptor and a noncompetitive antagonist of NMDA, produces a similar increase in NMDA-sensitive glutamate and kainate receptor binding in hippocampus 24 hours after a dose. These observations support the conclusion that blockade of glutamate-mediated transmission at the NMDA receptor selectively increases NMDA-sensitive glutamate receptor binding in CA1 of hippocampus and kainate binding in CA3 and dentate gyrus at putatively delayed time points. Several additional areas outside of hippocampus also showed receptor changes at 24 hours after MK801.
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  • 10
    ISSN: 1435-1463
    Keywords: Accumbens nucleus ; α-adrenoceptors ; dopamine receptors ; dorsal striatum ; entopedunular nucleus ; glutamate receptors ; hippocampus ; locomotion ; mouse ; muscarine receptors ; rotation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous work, based on systemic drug administration, has shown that neurotransmitter interactions between dopaminergic, adrenergic, glutamatergic and cholinergic systems are involved in locomotor control in mice. In an attemp to identify the target sites in the brain of these interactions, we have started a series of experiments, where the drugs are administered intracerebrally in mice. The locomotor threshold doses of the competitive NMDA antagonist AP-5 and the noncompetitive NMDA antagonist MK-801 were investigated by means of local application in the accumbens nucleus of monoamine-depleted and monoaminergically intact mice, respectively. The threshold dose of AP-5 was lower in depleted than in intact animals, whereas the threshold dose of MK-801 was lower in monoaminergically intact than monoamine-depleted mice. The locomotor effects of AP-5 and the AMPA-kainate receptor antagonist CNQX were registered in monaomine-depleted mice after local application in the accumbens or entopedunular nucleus (= medial pallidum). Both AP-5 and CNQX stimulated locomotor activity in the accumbens, but had no effects in the entopedunular nucleus. We have previously shown synergistic interactions with regard to locomotor stimulation in monoamine-depleted mice, between an NMDA antagonist and an α2-adrenoceptor agonist or a dopamine D1 agonist (all drugs given systemically). In the present study the α2-adrenoceptor agonist α-methylnoradrenaline was applied intracerebrally in combination with a subthreshold dose of MK-801 given intraperitoneally: Locomotor stimulation was produced after α-methyl-noradrenaline injection into the accumbens nucleus, but not after injection into the dorsal striatum, prefrontal cortex or thalamus. Likewise, local application of the D1 agonist SKF 38393, in combination with a subthreshold dose of MK-801 given intraperitoneally, point to an important role of the accumbens nucleus in motor control. Previous experiments based on systemic drug administration have also shown a synergistic interaction between a muscarine antagonist and an α2-adrenoceptor agonist in monoamine-depleted mice. Local application of the muscarine antagonist methscopolamine, in combination with the α2-adrenoceptor agonist clonidine given intraperitoneally, showed that the striatum, in this case both the ventral and dorsal parts of the striatum, is an important target for the muscarine antagonist. Unilateral injection of AP-5 into the accumbens nucleus of mice induces rotational behaviour: Previous findings have shown that the rotation is ipsilateral in monoaminergically intact animals, whereas monoamine-depleted animals rotate contralaterally. In addition, these findings have shown that dopamine D2 receptor stimulation seems to determine whether AP-5 will induce ipsilateral or contralateral rotation. In the present study we report further evidence for a crucial role of the D2 receptor in this respect. Finally, the rotational effects of AP-5 injected into the dorsal striatum or hippocampus were investigated: As after AP-5 application into the accumbens nucleus, monoaniinergically intact mice rotated ipsilaterally, whereas monoamine-depleted animals rotated contralaterally, following AP-5 application in the dorsal striatum or the hippocampus. The present data show that the accumbens nucleus has an important role in motor control. Both glutamatergic, muscarine cholinergic, dopaminergic and α-adrenergic systems are involved in the control of motor functions in the accumbens nucleus.
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