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J Glowinski

Publications and source records attributed to J Glowinski.

At least 433 records · Page 24Linked to original sources
PubMed1977

Regional differences in the sensitivity of cholinergic neurons to dopaminergic drugs and quipazine in the rat striatum.

Marked differences were found in the activity of choline acetylase (ChAc) in various discrete areas of the rat striatum. The richest cholinergic innervation was observed in the centrolateral part of the structure. A similar distribution was obtained by measuring acetycholine (ACh) levels in punches taken from frozen frontal serial slices. As revealed by the analysis of the topographical distributions of ChAc activity, ACh, 5-HT and DA, the regional cholinergic innervation differed markedly from that of aminergic terminals. Changes in ACh levels induced by drugs could be estimated in microdiscs of tissues punched from frozen slices. Apomorphine and haloperidol, which increased and decreased ACh levels respectively, induced similar effects in the various striatal areas examined. By contrast quipazine, a drug acting on 5-HT uptake and release and on serotoninergic receptors, selectively increased ACh levels in some areas of the striatum but not in others. The regional changes in ACh levels induced by quipazine were satisfactorily correlated with the regional distribution of 5-HT but not with that of DA. These results suggest that a limited population of striatal cholinergic neurons is under the inhibitory control of serotoninergic neurons. They also indicate that some striatal cholinergic neurons influenced by dopaminergic neurons are not controlled by serotoninergic neurons.

Acetylcholine↗
PubMed1977

Interdependence of the nigrostriatal dopaminergic systems on the two sides of the brain in the cat.

The release of [3H]dopamine in vivo was estimated in the left and right caudate nuclei of the cat during the continuous superfusion of the two structures with L-[3,5-3H]tyrosine by means of two "push-pull" cannulas. A lesion made in the left substantia nigra interrupted the release of [3H]dopamine in the ipsilateral caudate nucleus and was associated with a simultaneous increase in the release of [3H]dopamine on the contralateral side. The release of [3H]dopamine also decreased in the left caudate nucleus and increased in the right structure when dopamine was applied to the left substantia nigra which reduces the activity of the left dopaminergic pathway. A total of 120 estimations of the spontaneous release of [3H]dopamine were made simultaneously in the left and right caudate nuclei during periods characterized by a stable physiological state of the animals, and 76% of the estimations showed that an increase in the release of [3H]dopamine on one side corresponded to a decrease in the release of [3H]dopamine on the other side, and vice versa. These results demonstrate a close relation between the two nigrostriatal dopaminergic systems.

Action Potentials↗
PubMed1977

Retrograde axonal transport of 125I-tetanus toxin as a tool for tracing fiber connections in the central nervous system; connections of the rostral part of the rat neostriatum.

After previous studies had shown that 125I-tetanus toxin is taken up with high efficiency by all (adrenergic, sensory and motor)peripheral nerve terminals and that it is transported retrogradely by intraaxonal transport to the corresponding cell bodies, the present experiments were designed to investigate whether 125I-tetanus toxin could be used as a tool for retrograde tracing of fiber connections in the central nervous system and how the results obtained compared with other available retrograde tracing methods. Three to 12 h after injection of 125I-tetanus toxin into the rostral part of the nucleus caudatus of the rat, heavily labeled nerve cells were found in the substantia nigra zona compacta, in Forel field H2 and parts of the zona incerta, and in specific thalamic intralaminar nuclei (nucleus medialis pars lateralis and nucleus parafascicularis). Moderately labeled neurons were observed in the nucleus ventralis thalami and its dorsomedial part, in the nucleus raphe dorsalis and in the frontal, cingular and occipital cortex. Besides the labeling by retrograde transport, orthograde transport of radioactivity occurred in a striatonigral system. The high sensitivity and reliability of this method, even after injection of very small amounts of protein in a very small volume, represent important advantages over most of the commonly used tracing methods.

Animals↗
PubMed1977

Daily variations of various parameters of serotonin metabolism in the rat brain. I. Circadian variations of tryptophan-5-hydroxylase in the raphe nuclei and the striatum.

Daily changes in tryptophan-5-hydroxylase (TrH) activity have been studied in six different 5-HT-containing cell groups (B3, B4, B5, B6, B7, B8,) in the brain stem of rats maintained in a regular cycle of 12 h of light and 12 h of darkness. Significant circadian alternations of TrH activity were observed in most of the raphe nuclei tested, although the changes were not identical from one structure to another. The striatum showed daily variations in TrH activity in opposite phase to the nucleus raphe dorsalis which projects specific terminals into this area. Monoamine oxidase (MAO) activity was simultaneously estimated in these nuclei but did not exhibit and significant rhythm, suggesting a specific regulation of TrH. Total protein levels were also subject to daily changes.

Animals↗
PubMed1977

Daily variations of various parameters of serotonin metabolism in the rat brain. II. Circadian variations in serum and cerebral tryptophan levels: lack of correlation with 5-HT turnover.

Rats submitted to regular 12 h cycles of light and darkness for three weeks were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan levels were estimated in the fronto-parietal cerebral cortex. Tyrosine and free and total tryptophan levels in serum were estimated in parallel. Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues. The peaks of 5-HIAA levels were dectected during the lignt and dark periods respectively, the maximal fluctuations being seen between 17.00 h and 21.00 h, two times separating the light off. Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum was in opposite phase with that of tryptophan (free or total). The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum. Taking in consideration results obtained in previous studies 16,17 carried out in similar experimental conditions, it was concluded that the parallel increase in serum free tryptophan and in tissues 5-HIAA levels seen during the night were not related to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal at this time16.

Amino Acids↗
PubMed1977

Characteristics of dopamine and beta-adrenergic sensitive adenylate cyclases in the frontal cerebral cortex of the rat. Comparative effects of neuroleptics on frontal cortex and striatal dopamine sensitive adenylate cyclases.

Homogenates of frontal cerebral cortex of the rat were prepared from microdiscs punched out in areas rich in dopaminergic terminals. Under optimal assay conditions, dopamine (10-4 M) stimulated an adenylate cyclase present in these homogenates by 80-100%. This stimulation reached 200% when microdiscs were punched out from the medial part of the frontal cerebral cortex, adjacent to the forceps minor. Dopamine interacted with an homogeneous population of receptor sites which had an apparent affinity (KD) of 3.8 +/- 0.9 x 10-6 M (N = 4). The dopamine receptor was blocked by fluphenazine and phentolamine but had no affinity for pindolol, propranolol or L-isoproterenol. The affinities of several neuroleptics having different chemical structures were simultaneously determined on striatal and on frontal cerebral cortex dopamine sensitive adenylate cyclases. Fluphenazine was more potent in blocking the striatal than the frontal cerebral cortex dopaminergic receptors. In contrast, in all experiments, haloperidol had an higher affinity for the cerebral frontal cortex than for the striatal dopaminergic receptors. Thus, haloperidol was less effective than fluphenazine in blocking the striatal dopaminergic receptors, and equally potent than fluphenazine in inhibiting the frontal cerebral cortex dopamine sensitive adenylate cyclase. Chlorpromazine, thioridazine and clozapine had the same affinity for the two dopaminergic adenylate cyclase systems. L-isoproterenol interacted with an homogeneous population of beta-adrenergic receptor sites (KD = 3 +/- 2 X 10-7 M; N = 4) coupled with an adenylate cyclase distince from the dopamine sensitive adenylate cyclase. This beta-receptor had no affinity for dopamine or fluphenazine but was blocked by propranolol or pindolol. L-Norepinephrine was shown to stimulate both the dopamine (KD = 1.8 +/- 1 X 10-5 M; N = 4) and the beta-adrenergic (KD = 8 +/- 3 X 10-7 M; N = 4) sensitive adenylate cyclases. Thus, the L-norepinephrine effect was totally blocked in the combined presence of fluphenazine and pindolol.

Adenylyl Cyclases↗
PubMed1977

Effect of quipazine, a serotonin-like drug, on striatal cholinergic interneurones.

Quipazine (30 mg/kg i.p., 60 min), a serotonin-like drug increased ACh levels in the striatum (37%) but was without effect on the transmitter content in the hippocampus and the parietal cortex of the rat. Added in vitro(10(-5) M) or injected in vivo, quipazine did not affect choline acetylase and cholinesterase activities in striatal tissue. The drug effect on striatal ACh levels did not appear to be related to an interaction with dopamine metabolism. Indeed quipazine still increased striatal ACh levels after degeneration of the dopaminergic neurons had been induced by local injection of 6-OH-DA. p-Chlorophenylalanine (PCPA) pretreatment (300 mg/kg, 48 and 24 h before the experiment) definitely prevented the quipazine effect on ACh levels. This result suggested that the drug may partially act by its interference with 5-HT metabolism. 5-Methoxy-N,N-dimethyltryptamine (10 mg/kg, i.p., 30 min), a serotonergic agonist, induced a weak but significant increase in ACh levels. These data provide some preliminary evidence for the existence of an inhibitory control of the cholinergic interneurones by the serotonergic neurones projecting to the striatum. However, the lack of effect of 5-hydroxytryptophan (100 mg/kg i.p.), PCPA (2 x 300 mg/kg i.p.) and of Lilly 110 140 (10 mg/kg i.p.) and chlorimipramine (10 mg/kg i.p.), two potent inhibitors of 5-HT uptake, on striatal ACh levels indicate that further experiments are required to retain this hypothesis.

Acetylcholine↗
PubMed1977

Control of the release of newly synthetized 3H-5-hydroxytryptamine by nicotinic and muscarinic receptors in rat hypothalamic slices.

The effects of various cholinergic agonists and antagonists on the spontaneous release of newly synthetized 3H-5-HT were examined in rat hypothalamic slices. 3H-5-HT was measured in incubating medium at the end of a 30 min incubation carried out with L-3H-tryptophan in the presence of the various drugs tested. ACh (10(-5) M) in the presence of eserine (2 X 10(-4) M), and carbachol (10(-5) M) stimulated the release of 3H-5-HT. In contrast, oxotremorine (10(-5) M) reduced the 3H-amine release. The effect of carbachol was blocked by two nicotinic blockers, mecamylamine (10(-6) M) and d-tubocurarine (10(-6) M). It was not reduced by the muscarinic antagonists, atropine (10(-6) M) and scopolamine (10(-6) M). In fact, each of two antagonists added alone to the incubating medium enhanced 3H-5-HT release. The scopolamine (10(-6) M) stimulating effect on 3H-5-HT release was suppressed by d-tubocurarine (10(-6) M). Finally, the inhibiting effect of oxotremorine on 3H-5-HT release was not prevented by d-tubocurarine (10(-6) M) but was in the presence of atropine (10(-6) M) or scopolamine (10(-6) M). In the concentrations used in the release study, the cholinergic agonists and antagonists had no effect on the total formation of 3H-5-HT and 3H-5-HIAA from L-3H-tryptophan and on the accumulation of L-3H-tryptophan in tissues. In these concentrations, except for eserine, they did not affect the uptake of exogenous 3H-5-HT in hypothalamic synaptosomes (P2 fraction). These results suggest that cholinergic receptors of the muscarinic and nicotinic type are involved in the control of 3H-5-HT release; since the stimulation of the muscarinic and nicotonic cholinergic receptors resulted in an inhibition and an activation of 3H-5-HT release, respectively. As in the case of peripheral noradrenergic and central dopaminergic neurons the cholinergic receptors could be localized on serotoninergic terminals.

Animals↗