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J Glowinski

Publications and source records attributed to J Glowinski.

At least 415 records · Page 23Linked to original sources

Topographical distribution of dopaminergic innervation and dopaminergic receptors of the anterior cerebral cortex of the rat.

The quantitative topographical distribution of the dopaminergic innervation and the DA-sensitive adenylate cyclase were estimated in the anterior cerebral cortex of the rat. The high affinity uptake of [3H]DA and endogenous levels of DA were used as markers of the dopaminergic innervation. [3H]DA uptake, DA levels and DA-sensitive adenylate cyclase were estimated in microdiscs of tissues punched out from frozen serial frontal slices. The uptake of [3H]DA was measured on sucrose homogenates prepared from such microdiscs. The ventral part of the frontal cortex contained the highest DA concentration and DA-sensitive adenylate cyclase activity; the other structures rich in DA and in DA receptors were the cingular (close to the corpus callsoum) and the rhinal cortices. All of these cortical areas were rich in [3H]DA uptake sites. However, curiously, the dorsal part of the frontal cortex, which contained only moderate amounts of DA and of DA-sensitive adenylate cyclase, presented the highest number of [3H]DA uptake sites. Nevertheless, the uptake of [3H]DA in this region decreased by 60% after bilateral electrolytical lesions of the ventral tegmental area (A10 group). The parietal cortex was practically devoid of dopaminergic innervation and of DA-sensitive adenylate cyclase. The activity of the DA-sensitive adenylate cyclase in the frontal, cingular and rhinal cortices was 10-fold higher than that found in the striatum when compared to their respective DA levels.

Adenylyl Cyclases↗

[Lack of participation of cytoplasmic choline in the synthesis of acetylcholine in the striatal synaptosomes of the rat].

Synaptosomes prepared from Rat striatum were loaded with (14C) choline at 0 degrees C in the course of a 60 min. preincubation. After the removal, by washing, of the extracellular molecules, synaptosomes were incubated 5 min. at 37 degrees C in the presence of (3H) choline. The measurement of the amounts of (3H) ACh and of (14C) ACh formed allowed us to conclude that the acetylation of the molecules of choline was directly coupled to their passage through the synaptosomal membrane.

Acetylcholine↗

Release of dopamine in both caudate nuclei and both substantia nigrae in response to unilateral stimulation of cerebellar nuclei in the cat.

The effects of unilateral focal electrical stimulation of the deep cerebellar nuclei on the activity of the nigrostriatal dopaminergic neurons on both sides of the brain were examined in halothane anaesthetized cats. For this purpose, push-pull cannulae were inserted into both caudate nuclei and both substantia nigrae, and the release of [3H] dopamine ([3H]DA) continuously formed from [3,5-3H]L-tyrosine was estimated in superfusates. The unilateral electrical stimulation of the right cerebellar dentate nucleus induced a long-lasting increase in the release of [3H]DA in the left caudate nucleus and a simultaneous decrease in the release of [3H]transmitter in the right caudate nucleus. These changes were associated with opposite fluctuations in the release of [3H]DA from the corresponding substantia nigrae. Thus, the electrical stimulation of the right dentate nucleus induced a pronounced decrease in the release of the [3H]-amine in the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral substantia nigra, whereas the release in the ipsilateral substantia nigra was simultaneously increased. In contrast, the unilateral electrical stimulation of the right cerebellar fastigial nucleus resulted only in an increased release of [3H]DA in the ipsilateral (right) caudate nucleus, associated with a decreased release of the [3H]transmitter in the corresponding substantia nigra, whereas the activity of the contralateral (left) dopaminergic system was not significantly affected. These results support a direct functional interaction between the cerebellum and the basal ganglia. They also suggest that the release of DA from dopaminergic axonal terminals is inversely correlated to the extent of the transmitter release from dendrites.

Adrenergic Fibers↗

Dopamine uptake in serotoninergic terminals in vitro: a valuable tool for the histochemical differentiation of catecholaminergic and serotoninergic terminals in rat cerebral structures.

An in vitro method was developed to separately visualize dopaminergic, noradrenergic and serotoninergic terminals in the cerebral, hippocampal and cerebellar cortices of the rat, by means of the glyoxylic histochemical fluorescence method. Animals were pretreated with alpha-methylparatyrosine to deplete catecholamine stores. Thin vibratome sections were made and incubated in the presence of various exogenous amines and inhibitors of the catecholaminergic and serotoninergic transport systems. Experimental conditions insuring the best specificity were determined and the validity of the combined pharmacological and histochemical approach was further tested by using animals in which the cortical dopaminergic, noradrenergic or serotoninergic innervations were destroyed. Under the experimental conditions used, norepinephrine as well as alpha-methyl-norepinephrine were taken up in only noradrenergic and dopaminergic terminals. A separate visualization of the two systems was obtained by using specific uptake inhibitors. Dopamine was taken up not only in catecholaminergic but also in serotominergic terminals. The uptake of DA in serotoninergic fibers was inhibited by a specific inhibitor of the serotoninergic transport system or by the presence of serotonine in the incubating medium. The signification and the implications of thes results are discussed.

Animals↗

Release of dopamine evoked by electrical stimulation of the motor and visual areas of the cerebral cortex in both caudate nuclei and in the substantia nigra in the cat.

The effects of unilateral stimulation of the cerebral motor cortex and of the visual cortical area on the activity of the nigrostriatal dopaminergic neurons were examined in halothane-anesthetized cats. For this purpose, one push-pull cannula was inserted in each caudate nuclei and another one in the substantia nigra ipsilateral to the stimulated side. In all cases, the release of [3H]dopamine ([3H]DA) continuously formed from L-[3,5-3H]tyrosine was estimated in superfusates. Unilateral electrical stimulation of the cerebral motor cortex (area 4) induced a long-lasting and similar activation of [3H]DA release in both caudate nuclei. The activation of [3H]DA release in the contralateral side was selectively abolished after acute transection of the rostral part of the corpus callosum. This transection also suppressed the flexion of the contralateral forelimb induced by the stimulation. The activation of [3H]DA release could be related to the stimulation of corticostriatal neurons which may interact directly or indirectly with dopaminergic terminals in both caudate nuclei. Unilateral electrical stimulation of the visual cortex (areas 18 and 19) markedly stimulated the release of [3H]DA in the ipsilateral caudate nucleus. A slight effect was seen in the contralateral structure 20 min after the stimulation. These results are consistent with the existence of a main ipsilateral pathway originating from the visual cortex and projecting directly to the striatum. Both types of electrical stimulation immediately activated the release of [3H]DA in the ipsilateral substantia nigra. These effects were still seen 20 min after the stimulations. The activation of the dendritic release of [3H]DA could be related to the stimulation of a corticonigral projection. These results further indicate that the nigrostriatal dopaminergic neurons may be involved in sensory motor integration.

Animals↗

Inhibition of dopamine release in the cat caudate nucleus by nigral application of glycine.

"Encéphale isolé" cats were implanted with two push-pull cannulae, one in the left caudate nucleus and the other in the ipsilateral substantia nigra. L-3,5(-3)H-Tyrosine was introduced continuously into the caudate nucleus to study the release of 3H-DA. Glycine (10(-5)M) added to the superfusing medium of the push-pull cannula inserted into the substantia nigra reduced (25%) the spontaneous release of 3H-DA. Conversely, strychnine (10(-5)M) slightly stimulated the 3H-transmitter release. The inhibiting effect of glycine (10(-5)M) on 3H-DA release was no longer seen in the presence of strychnine (10(-5) M). The results support the hypothesis of a tonic glycinergic inhibitory control of the activity of the nigrostriatal dopaminergic neurons.

Animals↗

Paradoxical decrease of brain 5-HT turnover by metergoline, a central 5-HT receptor blocker.

Since metergoline (1-methyl-8-beta-carbobenzyloxy-aminomethyl-10-alpha-ergoline) is a potent 5-HT antagonist in peripheral organs, its possible blocking effects on 5-HT receptors in the rat brain were investigated. In vitro, metergoline inhibited both the specific high affinity binding of 3-H-5-HT onto synaptosomal membranes (IC 50 = 18 nM) and the stimulating effect of 10 micron 5-HT on the adenylate cyclase activity in colliculi homogenates from newborn rats (IC 50 = 12 micron. In vivo, the administration of metergoline (10 mg/kg i.p., 60 min before death) resulted in a significant decrease in the 3-H-5-HT binding capacity of synaptosomal membranes from the forebrain of adult rats. Taken together, these data clearly indicated that metergoline is a potent blocker of some serotoninergic receptors in the rat brain. Surprisingly, the changes in 5-HT turnover occurring in the brainstem and in the forebrain 1 h after metergoline (2-10 mg/kg) treatment were similar to those normally induced by a central 5-HT agonist: both the rate of 5-HT utilisation and that of 5-HT synthesis were significantly decreased. These changes were in contrast to the acceleration of 5-HT turnover induced by the administration of another potent central 5-HT antagonist, methiothepin. These results are discussed in relation to the possible existence of several types of serotoninergic receptors in the rat brain. It is possible that the positive feedback regulation of 5-HT turnover is triggered by the blockade of serotoninergic receptors sensitive to methiothepin, but not to metergoline.

Adenylyl Cyclases↗