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A Cudennec

Publications and source records attributed to A Cudennec.

12 recordsLinked to original sources
PubMed1997

Effects of amisulpride, an atypical antipsychotic which blocks preferentially presynaptic dopamine autoreceptors, on integrated functional cerebral activity in the rat.

Amisulpride, a benzamide derivative with an atypical neuroleptic profile relieves the negative symptoms of schizophrenia when administered at low doses (50-150 mg). In an attempt to define the anatomical substrates involved in this action we have studied the effects of amisulpride on regional cerebral glucose utilisation (RCGU) in the awake lightly restrained rat, by quantitative autoradiography using [14C]2-deoxyglucose ([14C]2-DG). Amisulpride was administered 1 h before [14C]2DG i.v. injection, at a dose of 5 mg/kg which resulted in a striatal D2 receptor occupancy of 10% similar to that induced by doses of this compound used for the treatment of negative symptoms of schizophrenia. Amisulpride induced significant RCGU increases in cortical areas, in visual relays, in auditory structures and in several limbic structures. The pattern of changes in RCGU seen with amisulpride clearly differs from that of haloperidol, given at a dose resulting in a similar occupancy of striatal D2 receptors (0.01 mg/kg), which was mostly ineffective. The amisulpride-induced activation of RCGU in specific brain areas involved in the control of cognitive functions and motivational and emotional behavior, may at least in part, explain the efficacy of this compound in the treatment of negative symptoms of schizophrenia.

Amisulpride↗
PubMed1997

Amisulpride: from animal pharmacology to therapeutic action.

Amisulpride is a benzamide derivative with a unique neurochemical and psychopharmacological profile. This compound has selective affinity for human dopamine D3 and D2 receptor subtypes in vitro (binding constant, K approximately 3 nmol/l) and blocks functional responses mediated by these receptors. In ex vivo binding studies, amisulpride is twice as selective for D3 as for D2 receptors. At low doses, it preferentially blocks presynaptic dopamine autoreceptors (increase in dopamine release in vivo in the rat olfactory tubercle, 50% effective dose, ED50 3.7 mg/kg), while postsynaptic dopamine receptor antagonism is apparent at higher doses (decrease in striatal acetylcholine levels, ED50 approximately 60 mg/kg). Anisulpride preferentially stimulates dopamine synthesis and displaces 3H-raclopride binding in vivo in the limbic system rather than the striatum. It antagonizes apomorphine-induced hypothermia in mice and amphetamine-induced hypermotility in rats at low doses (ED50 2-3 mg/kg), blocks apomorphine-induced climbing and spontaneous grooming in mice, blocks apomorphine-induced gnawing in rats at higher doses (ED50 19-115 mg/kg) and does not induce catalepsy at 100 mg/kg. The preferential antagonism by amisulpride of presynaptic D2/D3 receptors is reflected behaviourally in the potent blockade of apomorphine-induced effects mediated by dopamine autoreceptors (yawning and hypomotility: ED50 0.2 and 0.3 mg/kg, respectively) compared with those medicated by postsynaptic D2 receptors (e.g. gnawing: ED50 115 mg/kg). Moreover, low doses of amisulpride induce prohedonic (potentiation of food-induced place preference) effects in rats. The atypical neurochemical and psychopharmacological profiles of amisulpride may explain its therapeutic efficacy on both positive and negative symptoms of schizophrenia.

Amisulpride↗
PubMed1994

Effect of eliprodil, an NMDA receptor antagonist acting at the polyamine modulatory site, on local cerebral glucose use in the rat in the rat brain.

The present investigation examined the effect of eliprodil, an atypical NMDA receptor antagonist that acts at the polyamine modulatory site, on local cerebral glucose utilization using the quantitative autoradiographic 2-[14C]deoxyglucose method in the conscious rat. Eliprodil, at doses of 3, 10 and 30 mg/kg i.p., did not increase cerebral glucose use in any of the 82 different brain regions studied. However, in some of the regions examined, local cerebral glucose utilization was slightly reduced, the most pronounced decreases being measured in some extrapyramidal, sensorimotor and limbic areas (dentate gyrus, septum, lateral habenula, amygdala). This decrease in glucose utilization was dose-dependent: no significant change was noted after 3 mg/kg i.p. of eliprodil, while 18 (at 10 mg/kg, i.p.) and 29 (at 30 mg/kg, i.p.) regions displayed a moderate (20-25%) though significant decrease in glucose use. These data demonstrate that the pattern of alterations in glucose use produced by eliprodil is different from that induced by NMDA channel blockers or competitive NMDA receptor antagonists. The fact that blockade of the polyamine modulatory site is not associated with an activation of specific limbic circuits may explain why, at neuroprotective doses, eliprodil is devoid of those unwanted side effects (including intrinsic neurotoxicity on cortical neurons) associated with NMDA channel blockers.

Animals↗
PubMed1993

Effects of dorsal raphe nucleus stimulation on cerebral blood flow and flow-metabolism coupling in the conscious rat.

In the present study, we have investigated the effects of an activation of the ascending serotonergic pathway on the cerebral blood supply to a number (63) of well-defined neuroanatomical structures. To this end, we have measured the local cerebral blood flow during electrical stimulation of the dorsal raphe nucleus. Measurement of regional blood flow was performed in the conscious rat through the use of the [14C]iodoantipyrine autoradiographic technique. Stimulation of the dorsal raphe nucleus induced increases (> 15% compared to control) in cerebral blood flow in 17 structures of which statistical significance (P < 0.05) was achieved in nine; raphe stimulation significantly decreased flow in three regions. The greatest increases (+71 and +46%) were found in the frontal sensorimotor and posterior parietal cortices. Other increases were noted in relay stations of the extrapyramidal and limbic systems. Stimulation induced a decrease in two regions of the primary auditory system and in the lateral habenular nucleus. These results show that activation of the serotonergic pathway in the conscious rat effects regional cerebral blood flow heterogeneously, differing from the widespread increase in glucose utilization that we previously observed using the same experimental paradigm. Statistical analyses indicated that activation of the dorsal raphe nucleus resulted in a global modification of the flow-metabolism ratio. Moreover, in 19 out of 31 regions analysed, this ratio is significantly altered as compared to control. The dichotomy between raphe-induced changes in flow and glucose-metabolism could be explained by one or both of two hypotheses; firstly there could be a direct serotonergic innervation of cerebral resistance vessels; secondly, during raphe stimulation it could be that glucose use is not the primary determinant of tissue perfusion.

Animals↗
PubMed1988

Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. I. Effects of electrolytic or neurotoxic lesions of the dorsal and/or median raphé nucleus.

The regional cerebral metabolic effects of manipulations of the central serotonergic pathways are largely unknown. To address this topic, we have examined the consequences of electrolytic lesions of the rostral (median and/or dorsal) raphé nuclei on local cerebral glucose utilization (CMRglu) in the unanaesthetized rat brain. These studies were complemented by comparing control rats to rats that received prior intraventricular administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). CMRglu was determined in 56 neuroanatomically defined regions of the central nervous system in lightly restrained rats, by the quantitative autoradiographic 2-deoxyglucose technique. In all, 6 groups of rats were studied: sham-lesioned rats, rats with electrolytic lesion of the median, dorsal, or both these raphé nuclei; sham-injected and 5,7-DHT pretreated rats. The efficacy of both electrolytic and neurotoxic lesions was verified, in each animal, by neurochemical microassay of 5-hydroxytryptamine and its metabolite in samples of striatum, hippocampus and prefrontal cortex. Chronic interruption of serotonergic transmission was remarkable for the lack of resultant change in CMRglu. In rats that were subjected to electrolytic lesions of both median and dorsal raphé nuclei, discrete and significant decreases in CMRglu were observed in the red nucleus, substantia nigra and inferior olivary nucleus only. The rats subjected to 5,7-DHT treatment displayed no significant changes in CMRglu in all the brain regions analyzed, despite an 80% decrease in the concentrations of endogenous 5-hydroxytryptamine. Thus, it would appear that a viable serotonergic transmission is not a major determinant of integrated functional activity, even in those brain structures that receive rich raphé projections. Two hypotheses are advanced for this lack of change: firstly, the chronic reduction of 5-hydroxytryptamine levels is accompanied by compensatory changes in this or other neurotransmitter systems; secondly, serotonergic neurones may exert a phasic--rather than tonic--influence on glucose use in the mammalian brain.

5,7-Dihydroxytryptamine↗
PubMed1988

Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. II. Effects of electrical stimulation of the rostral raphé nuclei.

Although lesions of the rostral raphé nuclei have minimal effects on integrated functional activity, as studied by the 2-deoxyglucose technique, the repercussions of activating the ascending serotonergic pathways have yet to be reported in the literature. To examine this question, we studied the consequences of the electrical stimulation of the rostral (median or dorsal) raphé nuclei on local cerebral glucose use in the conscious rat. Glucose use was determined by quantitative autoradiography in 105 defined brain structures. Raphé stimulation increased glucose utilization in a number of well-defined structures and pathways, dorsal raphé stimulation being systematically more effective than median raphé stimulation. Of all the neocortical regions studied, only the somatosensory cortex displayed a columnar and laminar pattern of increased glucose use that was restricted to the somatotopic delineation of the rat's head and face. Increased glucose use was seen in almost all key elements of the extrapyramidal system with the notable exception of the caudate-putamen. The thalamic nuclei that were activated by rostral raphé stimulation included those that subserve the processing of somesthetic, accessory visual and limbic information. Raphé stimulation-induced decreases in local cerebral glucose use were never observed. Almost all of the induced changes could be prevented or obtunded by prior intraventricular administration of the serotonergic neurotoxin 5,7-dihydroxytryptamine, suggesting that the majority of the raphé-induced changes in integrated functional activity were mediated via the activation of serotonergic neurones. The magnitude and pattern of the increases in glucose use could not always be correlated with the regional density of serotonergic innervation nor with the distribution of 5-hydroxytryptamine receptor subtypes in the adult brain. However, the pattern of increased cortical glucose use closely matches the selective serotonergic innervation of the somatosensory cortex found in early postnatal development. Thus, it would appear that the 2-deoxyglucose technique reveals functional units in the cortex that are innervated at an early ontogenic stage. We postulate that the discrete and highly organized changes in integrated functional activity that follow raphé stimulation are due to serotonin acting in a phasic manner on restricted, possibly specialized, postsynaptic structures.(ABSTRACT TRUNCATED AT 400 WORDS)

5,7-Dihydroxytryptamine↗
PubMed1987

Effects of the GABA receptor agonist, progabide, upon local cerebral glucose utilization.

The effects of a specific GABA receptor agonist, progabide, have been examined on local cerebral glucose utilization through the use of the autoradiographic [14C]2-deoxyglucose technique in conscious rats. The intraperitoneal administration of progabide (80-320 mg.kg-1) resulted in a heterogeneous pattern of significantly reduced glucose utilization throughout the 50 discrete regions of the brain that were studied. Insignificant decreases in local cerebral glucose use were noted following the low dose of progabide (80 mg.kg-1). Following progabide (160 mg.kg-1), reductions of approximately 20% in glucose utilization were observed in most of the extrapyramidal system (substantia nigra, pars compacta and reticulata; globus pallidus; caudate nucleus), some thalamic nuclei (lateral geniculate body, anterior and ventrolateral thalamic nuclei), a number of areas related to the limbic system (cingulate cortex; amygdala; hypothalamus; lateral habenula; nucleus accumbens; dorsal hippocampus as well as the CA3 field) and the raphé nuclei. In contrast, layer IV of the neocortex, the cerebellum and cerebellar nuclei, displayed only minimal (10-15%) reductions in glucose utilization. At the highest dose (320 mg.kg-1) examined, progabide effected widespread though heterogeneously distributed decreases in glucose use. The overall pattern of decreased glucose use seen with progabide was different from that noted with previously studied GABA-mimetic drugs, such as muscimol, except for those changes observed in the extrapyramidal and sensory-motor areas for which similar dose-response relationships occurred. A significant correlation was observed between progabide-induced decreases in glucose utilization and in serotonin synthesis in a number of brain areas. The pattern of progabide-induced changes in integrated functional activity is compatible with its neurochemical spectrum and could indicate the loci at which its anticonvulsant, antidepressant and extrapyramidal activities are initiated.

Animals↗
PubMed1987

Serotonergic neuron stimulation modulates thalamocortical glucose use in the conscious rat.

We have studied the effects, in the conscious rat, of electrical stimulation of the dorsal or median raphe nuclei on integrated functional activity, as assessed by the quantitative 2-deoxyglucose autoradiographic technique. Stimulation of serotonergic neurons elicits metabolic changes in cortical and thalamic regions that are not limited to those structures known to receive the densest serotonergic innervation. The thalamic nuclei that are activated by raphe stimulation include those that subserve the processing of somesthetic, accessory visual, and limbic information. Raphe stimulation increased cortical glucose use in a laminar and columnar pattern, but only in a highly circumscribed region that corresponds to the somatotopic representation of the rat's face and head. These findings indicate that ascending serotonergic neurons play an important modulatory role in the regulation of thalamocortical glucose use, observations that may be of value in the understanding of the etiology and expression of classic migraine.

Animals↗
PubMed1984

Autoradiographic localization of dopamine receptors in the spinal cord of the rat using [3H]-N-propylnorapomorphine.

Dopamine receptors were localized autoradiographically in the rat spinal cord after in vitro labelling using 3H-N-propylnorapomorphine (NPA). The highest densities of 3H-NPA binding sites were found in the substantia gelatinosa and in a zone of the grey matter immediately ventral to the dorsal corticospinal tract. Other areas of the grey matter presented only moderate or low receptor densities while no 3H-NPA binding sites could be found in the white matter. The localization of 3H-NPA binding sites is compatible with a role for spinal cord dopamine in the processing of sensory information.

Animals↗
PubMed1980

Passive avoidence learning in the young rat.

A step-through locomotor passive avoidance task is described requiring the suppression of a spontaneous escape reaction from a cool toward a warm compartment in order to avoid an electric shock delivered in the warm side. We observed no lerning of this task at 9 days of age, a very low but significant level of acquisition at 11 days, a slow but progressive improvement of avoidance from the 13th until the 17th day when the adult capacity was achieved, and a marked increase in the rate between 17-20 days.

Aging↗
PubMed1977

Deficits in passive-avoidance learning following atropine in the developing rat.

The maturation of cholinergic inhibitory mechanisms that may be involved in passive-avoidance learning was studied in rats 14, 17, 21, 25, 28, and 34 days of age. Acquisition and extinction of the conditioned response were examined under saline and atropine sulfate (5 mg/kg). Learning was also tested following scopolamine hydrobromide injections (1, 4, 8 mg/kg) in rats 17 days of age and following alpha-methylatropine (5 mg/kg) in 17- and 34-day-old groups. In normal animals the rate of acquisition increased during ontogenesis, with a significant improvement between postnatal days 17 and 21, whereas the rate of extinction did not vary with age. Acquisition was impaired by atropine sulfate at all ages and even totally prevented in younger groups (14 and 17 days of age). It was also completely disrupted by scopolamine in 17-day-old rats. Extinction following acquisition under atropine was more rapid than after normal acquisition. Methyl-atropine was without effect. These results support the hypothesis of central cholinergic mechanisms involved in response suppression, already functioning in the rat 14 days of age and maturing mainly between the 17th and the 21st postnatal days.

Age Factors↗