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A Boireau

Publications and source records attributed to A Boireau.

53 records · Page 3Linked to original sources
PubMed1991

Differential effects of potassium channel blockers on dopamine release from rat striatal slices.

The effects of different potassium channel blockers on tritiated dopamine [( 3H]DA) release were investigated in rat striatal slices in the presence of pargyline and nomifensine (10 microM each). 4-Aminopyridine (4-AP; 10 and 30 microM) and 3,4-diaminopyridine (3,4-DAP; 30 microM) markedly increased the basal tritium outflow, whereas tetraethylammonium (TEA; 100-1000 microM) was without effect. The facilitating effect of 4-AP (10 microM) on spontaneous release was Ca(2+)- and K(+)-dependent. Moreover, the 4-AP-induced increase in spontaneous release was abolished in the presence of tetrodotoxin, indicating that voltage-dependent Na+ channels were involved in the release mechanism. 4-AP (10 and 30 microM) induced a dose-dependent decrease in K(+)-evoked [3H]DA release. This effect was confirmed with 3,4-DAP (30 microM). When striatal slices were depolarized with veratridine (5 microM), these two aminopyridines increased the evoked release of [3H]DA. TEA increased both K(+)- and veratridine-evoked [3H]DA release. These biochemical results are consistent with electrophysiological differences between the mechanism of action of aminopyridines and that of TEA.

4-Aminopyridine↗
PubMed1990

Effect of gamma-butyrolactone on the retrograde axonal transport of neurotensin in dopaminergic neurones.

gamma-Butyrolactone is a drug known to inhibit the flow of electrical impulses in dopaminergic neurones and to prevent dopamine release in the striatum. In this study, we investigated the effects of this compound on the retrograde transport of neurotensin in the nigrostriatal dopaminergic pathway. The amount of radioactivity measured in the substantia nigra after injection of iodinated neurotensin into the striatum and the time course of its accumulation were not found to be modified in gamma-butyrolactone-treated rats. We therefore conclude that the retrograde axonal transport of neurotensin in the nigrostriatal pathway is not affected by reduced dopaminergic firing or by inhibition of the striatal release of dopamine.

4-Butyrolactone↗
PubMed1990

Preferential decrease in dopamine utilization in prefrontal cortex by zopiclone, diazepam and zolpidem in unstressed rats.

This study has compared the effects of a cyclopyrrolone, zopiclone, a benzodiazepine, diazepam, and an imidazopyridine, zolpidem, on dopamine (DA) and DOPAC levels, and DA utilization (DOPAC/DA ratio) in rat striatum and prefrontal cortex. The endogenous levels of DA were significantly increased by both zopiclone (2.5, 10 and 40 mg kg-1 p.o.) and diazepam (10 and 40 mg kg-1 p.o.) in the prefrontal cortex, whereas striatal DA content was significantly increased only with the highest dose of diazepam (40 mg kg-1 p.o.). Diazepam (10 and 40 mg kg-1 p.o.) decreased cortical level of DOPAC more markedly than striatal levels, whereas zopiclone (40 mg kg-1 p.o.) only slightly decreased striatal DOPAC levels. Zopiclone and diazepam dose-dependently decreased DA utilization, an effect which was more marked in prefrontal cortex than in striatum. This result was confirmed with zolpidem, another benzodiazepine ligand. Zopiclone was most potent at decreasing DA utilization at the cortical level. The diazepam-induced decreases in DA metabolism and utilization were antagonized by Ro 15-1788, suggesting that the effects seen were mediated by specific benzodiazepine receptors. Thus, our results clearly show that ligands acting on the benzodiazepine receptor GABA receptor chloride ionophore complex can decrease the utilization of dopamine in unstressed rats. The preferential decrease in cortical DA utilization induced by benzodiazepine ligands may be compared to the well-known activation by stress of the mesocortical DAergic system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

In vivo determination of the profile of benzodiazepine ligands by comparing the inhibition of 3H-Ro 15-1788 binding to the modulation of cGMP levels in mouse cerebellum.

The in vivo effects of various benzodiazepine (BZD) ligands belonging to different chemical families were studied comparatively in mouse cerebellum using displacement of 3H-Ro 15-1788 binding and cGMP content as biochemical tools. It was possible to differentiate four classes of compounds with regard to these biochemical parameters. The first class of compounds such as diazepam and suriclone induced a net effect on in vivo 3H-Ro 15-1788 binding and a dose-dependent decrease of cGMP levels. A second class of drugs such as ZK 91296 and CGS 9896 showed in vivo activities in displacement studies but relatively small or moderate activities on cGMP levels. A third class was represented by Ro 15-1788 itself which prevented dose-dependently the in vivo 3H-Ro 15-1788 binding but was devoid of effect on cGMP levels. Finally, a fourth class of compounds (CGS 8216, FG 7142, beta-CCM and DMCM) showed in vivo displacement of 3H-Ro 15-1788 with concomitant increase of cGMP levels. The first class of compounds represents full agonists, the second class, partial agonists, the third class, the antagonist Ro-15-1788 itself, and the fourth class corresponds to inverse agonists. Thus it is proposed to use 3H-Ro 15-1788 binding and cGMP levels to differentiate in vivo BZD ligands acting on the BZD receptor/GABA receptor/chloride ionophore complex.

Animals↗
PubMed1988

Neurotensin effects on evoked release of dopamine in slices from striatum, nucleus accumbens and prefrontal cortex in rat.

The effects of neurotensin (NT) on the K+-evoked release of endogenous and tritiated dopamine in striatum and on 3H-dopamine in slices from nucleus accumbens and prefrontal cortex were investigated. In striatum, NT (1-1,000 nM) elicited a dose-dependent increase in endogenous and 3H-dopamine release. The dose-response curves were comparable with the two methods. Concerning the comparison of NT modulation of 3H-dopamine release in the three cerebral structures, the peptide induced a more marked effect in striatum with a maximal effect of 150% increase. In accumbens, NT (1-1,000 nM) potentiated the K+-evoked 3H-dopamine release, but in contrast with striatum, the plateau corresponded to a 50% increase. In prefrontal cortex, NT (1-1,000 nM) induced small but significant effects, with a maximal increase of 50% at 100 nM. Acetyl-NT (8-13) displayed an action similar to the natural peptide while NT (1-8) did not exhibit any effect, suggesting that the action of NT involved a receptor. The presence of tetrodotoxin did not alter the facilitating effects of NT in the three structures, indicating that interneurons were not involved in the action of NT. The comparison of the effects of NT showed that in terms of efficacy, NT induced an increase in dopamine release more marked in striatum than in nucleus accumbens and prefrontal cortex. These results are consistent with differences in NT receptors localization in these three dopaminergic structures.

Animals↗
PubMed1986

Enhancing effect of dopamine blockers on evoked acetylcholine release in rat striatal slices: a classical D-2 antagonist response?

The effects of chlorpromazine, pipotiazine, haloperidol, domperidone, sulpiride and SCH 23390 on the potassium-evoked release of [3H]acetylcholine [( 3H]ACh) were studied in rat striatal slices. All 5 dopamine (DA) antagonists with D-2 blockade efficacy induced an increase of [3H]ACh release whereas the specific D-1 antagonist SCH 23390 was devoid of significant effects. The maximal effect (about 100% increase) was obtained with haloperidol, pipotiazine and sulpiride but not with domperidone and chlorpromazine. Interestingly, sulpiride was found to exert an unexpected marked potency. The comparison of the activities of the 6 compounds on evoked ACh release to their affinities for D-2 receptors [( 3H]N-propylnorapomorphine binding sites) indicates that the pharmacological profile of the dopamine receptor implicated in the regulation of ACh release cannot be superimposed on that of the classical D-2 receptor. Participation of DA presynaptic receptors could however explain the differences in efficacy observed with the compounds studied.

Acetylcholine↗
PubMed1984

Suriclone, a new anxiolytic of the cyclopyrrolone family: evidence for possible interference with GABAergic systems.

The action of suriclone (R.P. 31,264), a new non-benzodiazepine compound of the cyclopyrrolone family with clinical anxiolytic activity was examined using biochemical and electrophysiological models supposed to be capable of revealing central GABAergic activity. Suriclone, which does not act directly on the gamma-aminobutyric acid (GABA) receptor (muscimol binding assay), markedly reduced the increase of striatal HVA level induced in the rat by a neuroleptic and decreased the cerebellar vermis cGMP content. Moreover, in the cat, suriclone was able to enhance dorsal root potential amplitude which reflects an increase of the presynaptic inhibition. In view of these results, a central GABAergic mechanism of action may be proposed for suriclone.

Animals↗
PubMed1983

Brain receptors and zopiclone.

Zopiclone (ZPC; RP 27,267), which is chemically unrelated to benzodiazepines (BZD), was found to have a similar pharmacological profile and to possess in man hypnotic activity similar to that of some BZD such as nitrazepam. It was, therefore, interesting to study the interaction of ZPC with rat brain receptors and specially with the so-called 'BZD receptors'. ZPC possesses in three rat brain regions a high affinity for BZD receptors: its Ki values measured against [3H]-flunitrazepam are 24 nM in the cerebral cortex, 31 nM in the cerebellum, and 36 nM in the hippocampus. No other brain receptors such as gamma-aminobutyric acid receptor, dopamine receptor, serotonin and noradrenergic receptors are reached by ZPC. Moreover, ZPC seems to bind only to brain BZD receptors and, contrarily to some BZD such as flunitrazepam, it does not reach the peripheral renal BZD-binding sites. The synthesis of [3H]-ZPC has permitted a more in-depth study of the interaction of ZPC with brain receptors. The high affinity of ZPC has been confirmed by equilibrium-binding studies (KD = 13 +/- 4 nM in rat hippocampus) and the study of the modulating effect of gamma-aminobutyric acid and barbiturates on ZPC binding has revealed some differences between ZPC and BZD. It could, therefore, be postulated that ZPC might bind in rat brain to sites which do not correspond exactly to BZD sites.

Animals↗
PubMed1982

Brain receptors and zopiclone.

Zopiclone (ZPC; RP 27,267), which is chemically unrelated to benzodiazepines (BZD), was found to have a similar pharmacological profile and to possess in man hypnotic activity similar to that of some BZD such as nitrazepam. It was, therefore, interesting to study the interaction of ZPC with rat brain receptors and specially with the so-called 'BZD receptors'. ZPC possesses in three rat brain regions a high affinity for BZD receptors: its Ki values measured against [3H]-flunitrazepam are 24 nM in the cerebral cortex, 31 nM in the cerebellum, and 36 nM in the hippocampus. No other brain receptors such as gamma-aminobutyric acid receptor, dopamine receptor, serotonin and noradrenergic receptors are reached by ZPC. Moreover, ZPC seems to bind only to brain BZD receptors and, contrarily to some BZD such as flunitrazepam, it does not reach the peripheral renal BZD-binding sites. The synthesis of [3H]-ZPC has permitted a more in-depth study of the interaction of ZPC with brain receptors. The high affinity of ZPC has been confirmed by equilibrium-binding studies (KD = 13 +/- 4 nM in rat hippocampus) and the study of the modulating effect of gamma-aminobutyric acid and barbiturates on ZPC binding has revealed some differences between ZPC and BZD. It could, therefore, be postulated that ZPC might bind in rat brain to sites which do not correspond exactly to BZD sites.

Animals↗
PubMed1976

In vivo release of 5-HT in the lateral ventricle of the rat: effects of 5-hydroxytryptophan and tryptophan.

The in vivo release of 5-HT was examined in the rat brain. For this purpose, the left lateral ventricle was perfused at a constant rate with an artificial CSF for several hours in animals anaesthetized with halothane. 5-HT was estimated in serial 1-h collected fractions. The amine was first isolated by adsorption on a Sephadex G-10 column and then assayed using the radioenzymatic method of Saavedra et al.37, slightly modified to improve its sensitivity. The quantity of 5-HT released spontaneously during the first hour fraction was 296 pg, it was lower (99 pg/h) in the following fractions. 5-HT released into the CSF may in great part originate from serotoninergic terminals localized in structures surrounding the ventricle. This was suggested by experiments in which exogenous [3H]5-HT or [3H]tryptophan were perfused through the lateral ventricle during a few hours. [3H]5-HT taken up or synthetized was mainly localized in structures surrounding the ventricular space. The acute injection of 5-hydroxytryptophan (100 mg/kg) induced an immediate important and long lasting increase of 5-HT release. In contrast the acute injection of tryptophan (100 mg/kg) led to a transient and moderate elevation of 5-HT release which was only detected during the second hour of perfusion. Curiously a similar pattern of transmitter release was observed following the constant intravenous infusion of the amino acid (70 mg/kg/h) except that the increase in 5-HT release was much more pronounced during the second hour than after the acute injection. Parallel experiments were made to determine the time course of the changes of free and total tryptophan levels in plasma and of those of tryptophan, 5-HT, and 5-hydroxyindoleacetic-acid (5-HIAA) in brain tissues, induced by the acute and long term administrations of tryptophan. Moreover the rate of 5-HT synthesis was estimated using the monoamine oxidase inhibition method 2 and 5 h after both tryptophan treatments in halothane anaesthetized rats. 5-HT levels and the synthesis rate of the transmitter were increased at 2 h (when both tryptophan treatments stimulated 5-HT release). Despite the presence of high tryptophan levels in plasma and tissues and of high 5-HT and 5-HIAA levels in tissues, the synthesis rate of 5-HT (as the 5-HT release) was similar to that of controls 5 h after the onset of tryptophan infusion. These results suggest that some relationships occurred between the changes in 5-HT SYNTHESIs and release after the first hour of perfusion. The absence of effects of tryptophan treatments on 5-HT release during the first hour of perfusion are also discussed.

5-Hydroxytryptophan↗
PubMed1975

Effects of halothane and nitrous oxide anaesthesia on 5-HT turn-over in the rat brain.

The effects of anaesthesia with halothane and nitrous oxide on the turn-over of 5-HT in the rat brain were analysed. The rate of 5-HT synthesis was estimated on the basis of 5-HTP accumulation following 5-HTP decarboxylase inhibition. Inhalation anaesthetics reduced the rate of 5-HT synthesis in the whole brain, this effect being particularly marked in the forebrain. In addition, the reduction of the rate of 5-HT synthesis was still detected after a large tryptophan loading indicating that halothane and nitrous oxide anaesthesia reduced the activity of tryptophan hydroxylase in vivo. The utilization of 5-HT was also delayed during anaesthesia since the rate of 5-HT disappearance following the inhibition of its synthesis at the decarboxylation step was decreased in the whole brain. In spite of this reduced turnover of 5-HT in the brain of rats exposed to inhalation anaesthetics, the 5-HIAA levels were permanently elevated. This was the result of a partial inhibition of the active elimination of the acidic metabolite from the brain during this kind of anaesthesia.

5-Hydroxytryptophan↗
PubMedDate not supplied

[The biochemical effects of a new antidepressive, metapramine (RP 19560) on activity of the dopaminergic and cholinergic systems of the rat striatum].

The effects of metapramine (R.P. 19,560) on dopaminergic and cholinergic activities were mainly studied in the rat striatum. Metapramine, contrarily to apomorphine, is devoid of in vitro affinity for dopamine receptors and does not modify in vivo, the utilisation of dopamine in the striatum. Moreover, metapramine does not modify the increase of dopamine utilisation induced by thioproperazine, a neuroleptic of the phenothiazine family. Consequently metapramine is devoid of direct or indirect effect on nigrostriatal dopaminergic system. Metapramine, like dopaminergic agonists, increases acetylcholine levels in the striatum. Moreover metapramine is inactive in cerebral cortex and hippocampus. Metapramine partly or completely antagonises the decrease of acetylcholine levels induced by two neuroleptics of the phenothiazine family (thioproperazine and prochlorperazine), by reserpine or an association of reserpine and alpha-methyl-p-tyrosine. Metapramine which possesses a clinical antidepressant efficacy could be indicated for correction of extra-pyramidal side effects induced by neuroleptics or observed in parkinsonism.

Acetylcholine↗