Clozapine increases dopamine release in prefrontal cortex by 5-H(1)A receptor activation

Clozapine (1-10 mg/kg s.c.) produces a selective increase in dopamine release in rat prefrontal cortex which is, in large part (similar to 50%), mediated via activation of 5-HT1A receptors. Clozapine is a moderately potent, partial 5-HT1A receptor agonist and activation of 5-HT1A receptors may contribute to its efficacy against negative symptoms and reduced extrapyramidal side effect liability. Agonist affinity for 5-HT1A receptors could thus be a desirable feature in the design of new antipsychotics. (C) 1997 Elsevier Science B.V.