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

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Summary

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.

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  1. Department of Biology, Neuropharmacology Unit, L.E.R.S. — Synthélabo, 31, av. P. V. Couturier, F-92220, Bagneux, France

    P. Worms & K. G. Lloyd

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Worms, P., Lloyd, K.G. Biphasic effects of direct, but not indirect, GABA mimetics and antagonists on haloperidol-induced catalepsy. Naunyn-Schmiedeberg's Arch. Pharmacol. 311, 179–184 (1980). https://doi.org/10.1007/BF00510257

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