The role of the 5-HT2 receptor in the regulation of sexual performance of male rats

Abstract

The present studies have attempted to evaluate the role of 5-HT2 receptors in the regulation of sexual behavior of male rats by determining the effects of 5-HT2 receptor antagonists, pirenperone, LY53857 and LY281067, and a 5-HT2 receptor agonist, DOI. The administration of 1 mg/kg s.c. pirenperone produced a total suppression of ejaculatory response and lower doses had no effect. However, the administration 0.1 mg/kg s.c. of either LY53857 or LY281067 restored ejaculatory capacity to rats that were unable to ejaculate and produced significant decreases in ejaculatory latency in rats with full sexual capacity. Although all of these agents are 5-HT2 antagonists, LY53857 and LY281067 lack the additional monoaminergic activity of pirenperone. Since the effects of pirenperone were opposite from the effects of the selective 5-HT2 antagonists, the suppressive effects of this agent were probably related to its other monoaminergic activity e.g. alpha 1 antagonist activity. This proposal was supported by the observation that the administration of prazosin, an alpha 1 antagonist, significantly increased ejaculatory latency and suppressed the stimulatory effects of LY53857. In contrast to the stimulatory effects of the selective 5-HT2 antagonists, the administration of DOI, resulted in a suppression of sexual performance, which was blocked by pretreatment with LY53857.