5-HT1B agonists induce anorexia at a postsynaptic site.

Ru 24969 and two other putative 5-HT1B agonists 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl) phenyl]piperazine (TFMPP) and RU 24969 dose-dependently decreased food intake over 4 h (and in the case of RU 24969 also over 24 h) in free-feeding male Sprague-Dawley rats. Decreasing the doses of the agonists below the range eliciting anorexia did not cause hyperphagia. The anorexic effect of RU 24969 over 4 h was antagonised by metergoline, (-)pindolol and (+/-)cyanopindolol, but not by ketanserin, spiperone or haloperidol. Metergoline and (+/-)cyanopindolol also antagonised the anorexic effect of RU 24969 over 24 h. This data is consistent with an action mediated by 5-HT1B receptors. Locomotor activity induced by RU 24969 was markedly antagonised by haloperidol despite its lack of effect on the anorexic response. Persistence of the anorexic effect of RU 24969 after p-chlorophenylalanine (pCPA) pretreatment suggests that 5-HT1B agonists induce anorexia at a postsynaptic 5-HT receptor.