RESTORING NORMAL FREQUENCY AND DURATION OF FEMALE SEXUAL BEHAVIOR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To improve our understanding of serotonin-related neural mechanisms regulating female sexual response in marmosets in order to develop more appropriate clinical intervention for sexual hypofunction in women. Sexual dysfunction affects an estimated 43% of women. Currently there are no approved drug therapies for this disorder. Safety concerns about hormonal treatment with estrogens and progestogens motivates the search for non-steroidal pharmoacotherapy. The serotonin (5-HT) neuronal system has been implicated in regulating sexual behavior in a range of female mammals, including humans and nonhuman primates, but the mechanisms involved are not well understood. We developed a model system with female common marmosets to demonstrate that flibanserin stimulation of 5-HT1A (agonist) and 5-HT2A (antagonist) postsynaptic receptors increases male attention to female genital area without altering female sexual behavior, while chronic stimulation of pre- and post-synpatic 5-HT1A receptors by 8-OH-DPAT diminishes female sexual receptivity. Flibanserin also encourages a positive dynamic (allogrooming) between treated females and their male pairmates, in contrast to the negative dynamic engaged by 8-OH-DPAT (aggression, sexual rejection of the male). Postsynaptic action of flibanserin may be preferentially focused on the prefrontal cortex. As there were no observed behavioral differences between females receiving estradiol or no hormone, flibanserin may counteract low sexual desire in women, before or after menopause, by supporting positive interactions with their partner. This research used WNPRC Assay Services and Animal Services. Publications are pending.