Clozapine acts as a 5-HT2 antagonist by attenuating DOI-induced inhibition of male rat sexual behaviour.

Evidence has been reported that clozapine may derive part of its therapeutic effects in treatment-resistant schizophrenic patients by interacting with the serotonin system. Among the few behavioural models available to test the hypothesis of an interaction of clozapine with 5-HT2 receptors, male rat sexual behaviour is particularly useful, since in this behaviour 5-HT1A and 5-HT2 receptors have opposite functions. Stimulation of 5-HT1A receptors facilitates ejaculatory behaviour and stimulation of 5-HT2 receptors inhibit ejaculation. In the present study, male rat sexual behaviour was depressed by treatment with DOI (1.0 mg/kg), a selective 5-HT2 receptor agonist. The depressive effect of DOI was attenuated by the administration of clozapine (0.1-1.0 mg/kg) in doses that by themselves did not significantly affect sexual behaviour. It was concluded that clozapine in the male rat sexual behaviour model may be interpreted as serving as a 5-HT2 antagonist.