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.
Klint
T
T
Department of Psychology, University of Göteborg, Sweden.
Larsson
K
K
D000818:Animals; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D012702:Serotonin Antagonists; D003024:Clozapine