Serotonergic regulation of female sexual function in a non-human primate: The effects of chronic serotonin-1A-receptor agonists on gene expression in the marmoset brain.

Yves Aubert

My doctorate research targets the role of the central serotonin (5-HT) neurotransmitter system in the regulation of female sexual function. Pharmacological modulation of 5-HT neurotransmission is a common cause of diminished female sexual activity, and a majority of patients prescribed selective serotonin reuptake inhibitors (SSRIs) experience a treatment-induced detriment in sexual satisfaction. Studies in rodents have shown that the 5-HT1A, 5-HT2A/C, and 5-HT3 receptors are implicated in the occurrence of lordosis behavior, the most frequently used parameter to quantify female sexual receptivity in rodents. While these studies provide valuable insight into the receptor specificity through which 5-HT modulates female sexual behavior in rodents, knowledge of the neurobiological substrate that underlies female sexual function remains sparse, particularly in primates.

In my previous laboratory at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison, U.S.A., we have developed a model in the common marmoset monkey to study female sexual behavior in order to investigate both stimulatory and inhibitory effects of exogenous compounds on female sexual responses. In contrast to most non-primate mammals, female primates are generally receptive to a male’s sexual advances throughout their ovarian or menstrual cycles and continue to display sexual behavior after ovariectomy. There, I have investigated the chronic effects of 8-OH-DPAT, a 5-HT1A agonist, and flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, in behavioral, neuroendocrine, and functional brain imaging experiments in ovariectomized female marmoset monkeys.

At the Division of Medical Pharmacology at Leiden University, I am conducting a gene expression study under supervision of Dr. Nicole Datson and Prof. Ron de Kloet. This study entails a large-scale gene expression experiment using laser-microdissection techniques and the first marmoset-specific DNA microarray (EUMAMA) that was recently developed by Dr. Datson. Analyzing the brains of the same female marmosets that were studied for behavior, endocrine function, brain activity and in vivo 5-HT receptor and transporter binding, I aim to determine the effects of chronic 8-OH-DPAT administration on gene expression profiles in brain subregions that are involved in the neural circuitries regulating female sexual behavior and 5-HT neurotransmission. I expect to detect gene clusters in anatomical subregions of the brain that play a key role in the regulation of female sexual function and to gain novel insight into the genomic mechanisms through which 8-OH-DPAT exerts its effects on female sexual behavior.