Differential effects of acute administration of haloperidol and clozapine on ethanol-induced ascorbic acid release in rat striatum

Antipsychotic drugs were initially considered to act predominantly through their antagonism at dopamine D₂-like receptors. However, reports have demonstrated that the typical neuroleptic drug haloperidol and the atypical neuroleptic drug clozapine showed differential actions in clinical, behavioral and biochemical studies. Since ascorbic acid has a potential usefulness in psychological therapeutics, the present study investigates the actions of these two drugs on ethanol-induced ascorbic acid release in the striatum in order to help explain the different mechanisms of these drugs. The results showed that clozapine, at the doses of 15 and 30 mg/kg, i.p., had no effect on basal ascorbic acid release. However, a synergistic tendency at a dose of 15 mg/kg and a significant synergism at a dose of 30 mg/kg were observed on ascorbic acid release when clozapine was used with ethanol. In contrast, haloperidol, at the doses of 0.5, 1.0 and 2.0 mg/kg, i.p., administered alone did not affect the basal release of striatal ascorbic acid, and when used together with ethanol had neither a potentiating nor an antagonizing effect on ethanol-induced ascorbic acid release. Chlorpromazine, a nonselective dopamine receptor antagonist, at the dose of 5 mg/kg, i.p., affected neither the basal nor the ethanol-induced ascorbic acid release. Ritanserin, a 5-HT₂ receptor antagonist, at the dose of 1 mg/kg, s.c., significantly antagonized ethanol-induced ascorbic acid release. These results demonstrate that clozapine dose-dependently potentiates the stimulatory effect of ethanol on striatal ascorbic acid release and this effect of clozapine may not be related to its dopamine D₂ receptor antagonism. Copyright (C) 2000 Elsevier Science B.V.