Biphasic effects of direct, but not indirect, GABA mimetics and antagonists on haloperidol-induced catalepsy

Naunyn Schmiedebergs Arch Pharmacol. 1980 Mar;311(2):179-84. doi: 10.1007/BF00510257.

Abstract

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.

MeSH terms

  • Allylglycine / pharmacology
  • Animals
  • Apomorphine / pharmacology
  • Behavior, Animal / drug effects
  • Catalepsy / chemically induced
  • Catalepsy / physiopathology*
  • Drug Interactions
  • GABA Antagonists
  • Haloperidol / pharmacology*
  • Humans
  • Male
  • Muscimol / pharmacology
  • Rats
  • Stereotyped Behavior / drug effects
  • gamma-Aminobutyric Acid / physiology*

Substances

  • GABA Antagonists
  • Allylglycine
  • Muscimol
  • gamma-Aminobutyric Acid
  • Haloperidol
  • Apomorphine