Classical and non-classical neuroleptics induce supersensitivity of nigral GABA-ergic mechanisms in the rat.

Abstract

The present study compared the ability of neuroleptic and non-neuroleptic agents to modify the sensitivity of nigral, GABA-sensitive, non-dopaminergic efferents in the rat after sub-chronic administration. Pre-treatment with haloperidol or clebopride, 1.0 mg/kg PO for 10 days, induced supersensitivity to the behavioural effects of unilateral intranigral muscimol, 5.0 ng, on withdrawal day 1. This effect was no longer significant in other rats tested on withdrawal day 7. In contrast, similar pre-treatment with sulpiride, 20 mg/kg PO, led to significantly enhanced responses to intra-nigral muscimol on both withdrawal days. Pre-treatment with clozapine, 20 mg/kg, or thioridazine, 12 mg/kg PO, did not lead to supersensitivity on withdrawal day 1, but did so on withdrawal day 7. Pre-treatment with amitriptyline, 20 mg/kg PO, or metoclopramide, 1.0 mg/kg PO, failed to result in supersensitivity on either withdrawal day. The data confirm previous biochemical and behavioural findings suggesting that repeated administration of neuroleptics can induce nigral GABA-ergic supersensitivity in the rat, but demonstrate that this action is not an exclusive property of classical, cataleptogenic agents.