5-HT2 receptors and paced mating behaviour in the female rat

This work was carried out at the Laboratory for Neuropsychiatry, Copenhagen University Hospital, and Department of Pharmacol- ogy, University of Copenhagen. Previous studies have demonstrated the importance of 5-HT2A and 5-HT2C receptors in the regulation of female rat sexual behav- iour. In general, most studies on sexual motivation in the female rat have applied test conditions where the male paced the copulatory activity. However, recent studies indicate that only self-paced mat- ing is rewarding to the female rat. The present work investigated the role of 5-HT2A and 5-HT2C receptors in regulation of sexual motiva- tion in the female rat using a paced mating set-up in which the fe- male has the possibility to escape from the male during copulation. This test situation more closely resembles naturalistic conditions than does the more often used male-paced models. The results support the hypothesis that 5-HT2A and 5-HT2C re- ceptors are important in the regulation of female rat sexual motiva- tion. Stimulation of 5-HT2A receptors with the in vivo 5-HT2A re- ceptor agonist, DOI, facilitated sexual motivation. This effect was attenuated by administration of nefazodone, which has in vivo 5- HT2A receptor antagonist activity. In contrast, stimulation of 5- HT2C receptors with the in vivo 5-HT2C receptor agonist, MK-212, inhibited sexual motivation. This finding is in contrast to previous studies reporting facilitated lordosis behaviour following MK-212 treatment. The effects of MK-212 on paced mating behaviour were attenuated by olanzapine, which has in vivo 5-HT2C and 5-HT2A re- ceptor antagonist activity. Hence, the present work demonstrated the importance of appro- priate test methods in the study of female rat sexual behaviour. Fur- thermore, the results indicate opposite functions of 5-HT2A and 5- HT2C receptors in the regulation of female rat sexual motivation.