Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder

Abstract

Hypoactive sexual desire disorder (HSDD) is the most reported sexual dysfunction among premenopausal women worldwide. Bremelanotide, trade name Vyleesi, has been approved by the United States Food and Drug Administration to treat HSDD. However, despite approval, very little is known about its neurobiological mechanism of action. In this study, we utilized a female Syrian hamster model to investigate the effects of bremelanotide on melanocortin receptor expression in the mesolimbic dopamine system and sexual reward. We found that the majority of melanocortin 3 and 4 (MC4R) receptor mRNA is expressed in dopamine neurons in the ventral tegmental area (VTA). Fewer neurons express MC4R in the nucleus accumbens (NAc) or dorsal striatum, where they rarely colocalize with neurons expressing dopamine D1 or D2 receptors. Instead, MC4R mRNA is expressed in nucleus accumbens interneurons. Neither the low nor the high dose of bremelanotide had an effect on the expression of melanocortin receptor mRNA in the mesolimbic dopamine system. Finally, sexual experience resulted in a conditioned place preference (CPP) in female Syrian hamsters, though bremelanotide treatment failed to enhance sexual reward in this test. The results of this study are discussed in conjunction with similar studies in rats, with the conclusion that bremelanotide does not act on the VTA-NAc reward circuit and does not enhance the rewarding effects of sexual interactions.

Keywords: Melanocortin; Motivation; Nucleus accumbens; Sex; Social reward; Ventral tegmental area; Vyleesi.