Conditioned place aversion induced by 5-HT1c receptor antagonists

Abstract

A place-conditioning procedure was used to investigate the affective properties in rats of non-selective serotonin receptor antagonists (mianserin, eltoprazine and ketanserin) differing from each other by their affinity for 5-HT1C and 5-HT2 receptors among others. At the highest dose tested (10 mg/kg, i.p.), the mixed 5-HTlC /5-HT2 receptor antagonist mianserin produced a significant place aversion to the drug-paired compartment. The 5-HT1B receptor agonist/5-HT1C receptor antagonist eltoprazine induced a place aversion at doses of 1 and 10 mg/kg. In contrast, the 5-HT2 receptor antagonist ketanserin produced neither place aversion nor place preference at the doses tested (1 or 10 mg/kg, i.p.). The preferential 5-HT1C receptor agonist mCPP was given prior to mianserin or eltoprazine administration. mCPP (1 mg/kg, i.p.) significantly prevented the conditioned place aversion produced by mianserin or eltoprazine, without exhibiting any aversive or rewarding effect by itself. These results suggest that acute 5-HT1C receptor blockade is involved in the production of aversive effects of mianserin and eltoprazine.