Biphasic effects of direct, but not indirect, GABA mimetics and antagonists on haloperidol-induced catalepsy.
At very low doses the GABA agonists SL 76002 and muscimol diminish haloperidol-induced catalepsy. At somewhat higher doses these compounds potentiate catalepsy. Biphasic effects on DA-receptor mediated functions have previously been noted with bicuculline and picrotoxinin. In contrast, manipulation of GABA levels by enzyme inhibition induced only a monophasic effect on dopamine-mediated behaviour. The potentiation of GABA levels by enzyme inhibition induced only a monophasic effect on dopamine-mediated behaviour. The potentiation of haloperidol-induced catalepsy by GABA mimetics is also observed with dipropylacetate, delta-aminovaleric acid and gamma-acetylenic GABA. This GABA-mimetic potentiation of catakepsy was blocked by the coadministration of bicuculline. These results confirm and extend the hypothesis that GABA-neurons influence DA neuron function. Furthermore they suggest that more than one group of GABA receptors influence directly and/or indirectly DA neuronal function, with different resultant effects.
D000501:Allylglycine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D004347:Drug Interactions; D018756:GABA Antagonists; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D000501:Allylglycine; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D006220:Haloperidol; D001058:Apomorphine