IN VIVO ACTIONS OF CLOZAPINE AND HALOPERIDOL ON TURNOVER RATE OF ACETYLCHOLINE IN RAT STRIATUM

The authors have measured acetylcholine (ACh) content and turnover rate (TRach) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 μmol/kg) and haloperidol (10 μmol/kg) reverse the decrease in striatal TRach elicited by apomorphine (11 μmol/kg) while each antipsychotic affects the steady state and the TRach in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRach; clozapine (15 and 30 μmol/kg) neither decreases the content of ACh nor changes the TRach in striatum. Moreover, 60 or 90 μmol/kg of clozapine causes a 40% decrease in ACh content without affecting the TRach. Clozapine, but not haloperidol, antagonizes the increase in ACh content and the decrease in TRach elicited by arecoline (64 μmol/kg) and oxotremorine (9 μmol/kg) in striatum. Clozapine resembles trihexylphenidyl (14 μmol/kg) and benztropine (12 μmol/kg) because it decreases the ACh content of striatum without changing the TRach. Moreover, clozapine and benztropine reverse the increase in striatal TRach elicited by haloperidol. The increase in striatal TRach elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.