Abstract
The rate of synthesis of acetylcholine, estimated from the rate of incorporation of intravenously administered choline (methyl- 3H) into acetylcholine, was at least three times greater in the corpus striatum than in the cortex of rats killed by microwave irradiation. Administration of chlorpromazine (10 mg/kg) orally to rats induced a decrease in the concentration of acetylcholine in the corpus striatum, but did not affect either the concentration of acetylcholine in the cortex or its rate of synthesis in either brain region, as measured 3 hr after treatment. In contrast to the effect of chlorpromazine, however, treatment with clozapine (100 mg/kg, p.o.) lowered the level of acetylcholine in both the corpus striatum and cortex, and reduced its rate of synthesis in these regions of the brain. The doses of clozapine and chlorpromazine that produced these dissimilar effects on metabolism of acetylcholine did induce equivalent changes in both the rate of avoidance responding and the metabolism of striatal dopamine in rats. The results suggest that clozapine reduces cholinergic neuronal activity in brain. This effect of clozapine may explain the lack of extrapyramidal side effects in psychotic patients treated with the drug.
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