Flibanserin Treatment Increases Appetitive Sexual Motivation in the Female Rat

Introduction. Flibanserin is a mixed 5-HT1A agonist/5-HT2A antagonist that has been developed for the treatment of hypoactive sexual desire disorder in women. Aim. To assess the acute and chronic doseresponse effects of flibanserin on measures of sexual desire and copulation in ovariectomized rats primed with estradiol benzoate (EB) alone or in combination with progesterone (P). Methods. In Experiment 1, sexually experienced ovariectomized (OVX) rats at one testing site were rendered fully sexually receptive with EB+P priming and tested weekly with a sexually active male in bi-level pacing chambers following daily flibanserin treatment for 28 days. In Experiment 2, sexually experienced OVX rats at a different testing site received EB alone and were tested weekly with sexually active males following daily flibanserin treatment. Main Outcome Measures. Female appetitive behaviors (solicitations, hops and darts, anogenital investigations), defensive behaviors, pacing, lordosis, and male copulatory responses (intromissions and ejaculations) were measured during each 30-minute copulation test. Results. Acute flibanserin or 1 week of chronic flibanserin treatment did not modify sexual responses in fully (EB+P) or partially (EB-alone) primed females. After 2 weeks of chronic treatment, fully primed females displayed significantly more solicitations than the three other groups. After 3 weeks of chronic treatment, a significant increase in female solicitations was observed in both hormone-treatment groups. Conclusion. This study shows the first evidence that chronic, but not acute, flibanserin treatment augments appetitive sexual behaviors in OVX female rats primed with EB+P or EB alone. Given the positive effect of flibanserin in clinical trials, these results confirm previous reports that solicitations in the female rat are a predictive animal model of human female sexual desire.