DOI-induced inhibition of copulatory behavior in male rats: reversal by 5-HT2 antagonists

Relatively little is known regarding the role of 5-HT2 receptor activity in male rat sexual behavior. Previous work has yielded equivocal results, and both facilitation and inhibition of copulation have been reported to follow administration of selective 5-HT2 antagonists. In the present series of experiments, the ability of a variety of 5-HT2 antagonists to block inhibition induced by the 5-HT2/5-HT1C agonist DOI was examined. Systemic ritanserin, pirenperone and ketanserin all potently blocked DOI-induced (1.0 mg/kg SC) inhibition of mounts, intromissions and ejaculations. None of these drugs influenced the sexual behavior of the male rats when given alone in doses that effectively blocked DOI-induced inhibition. In addition, unlike ritanserin and ketanserin, pirenperone produced a biphasic effect on DOI-induced inhibition, exhibiting a diminished blockade at higher doses. This may be due to activity at receptors other than 5-HT2. Overall, the present data suggest that activity at 5-HT2 receptors mediates an inhibition of male rat sexual behavior.