Effects of haloperidol and low dose clozapine on the acetylcholine turnover rate in rat forebrain structures

The contents of acetylcholine and choline as well as the acetylcholine turnover rates were measured in olfactory tubercle, nucleus accumbens and striatum of rats receiving haloperidol and low dose clozapine intraperitoneally. Both haloperidol (1 mg/kg) and clozapine (1.25 mg/kg) led to an increase in the acetylcholine turnover in the mesolimbic nucleus accumbens and olfactory tubercle. However, the acetylcholine turnover in the striatum was affected differently by each antipsychotic. Whereas haloperidol elicited an increase in the acetylcholine turnover, the atypical neuroleptic clozapine failed to change this parameter in striatum. It can be concluded that haloperidol increases the acetylcholine turnover in both striatum and mesolimbic areas by blocking dopamine receptors localized at cholinergic interneurons. In contrast, it may be speculated that a low dose of clozapine appears to modulate the cholinergic activity by a preferential serotonin antagonist action.