[Interactions of GABAergic and catecholaminergic neurotransmissions. Effects of dopaminergic and noradrenergic agonists and antagonists on GABA turnover].
The effects of specific D1 and D2 agonists and antagonists on GABA turnover in four brain structures have been studied. GABA turnover was estimated by measuring the accumulation of GABA after GABA-T inhibition with gabaculine. Stimulation of DA receptors by apomorphine, a mixed D1 and D2 agonist or by (+/-)2-(N-phenylethyl-N-propyl)amino-5-hydroxytetraline, a selective agonist of D2 receptors, dose-dependently reduced GABA turnover. Both agonists had no effect on GABA levels. S(-)sulpiride, a selective D2 antagonist, had no effect on either GABA levels or GABA turnover. However, sulpiride antagonized the reduction of GABA turnover produced by apomorphine or (+/-)2-(N-phenylethyl-N-propyl)amino-5-hydroxytetraline. By contrast, SKF 38393, a selective D1 agonist, did not appear to influence GABA-mediated inhibitory neurotransmission. SCH 23390, a D1 antagonist, which by itself had no effect on GABA levels and only slightly decreased GABA turnover, did not antagonize the effect of apomorphine. On the contrary, SCH 23390, slightly, but significantly increased the reduction in GABA turnover produced by apomorphine. Furthermore, idaxozan, an alpha 2-antagonist, antagonized the reduction of GABA turnover produced by the alpha 2-agonist clonidine, but did not prevent the effect of apomorphine on GABA turnover. Thus, the tonic inhibition exerted by DA on GABA-mediated neurotransmission seems to be mainly controlled by D2 receptors.
Bernasconi
R
R
Laboratoires de recherche biologique, Ciba-Geigy Ltd, Bâle, Suisse.
Steulet
A F
AF
Aryee
D
D
Martin
P
P
Leonhardt
T
T
Bischoff
S
S
Maitre
L
L
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D013469:Sulpiride / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D001058:Apomorphine
Interactions entre les neurotransmissions GABAergique et catécholaminergique. Effets d'agonistes et d'antagonistes dopaminergiques et noradrénergiques sur la vitesse de renouvellement du GABA.