Abstract
Low levels of desire and arousal are the primary sexual dysfunctions in women, necessitating neurobiological studies of sexual motivation in female animal models. As the mesocorticolimbic system is a primary neural circuit underlying sexual motivation, the goal of this study was to test the hypothesis that medial prefrontal cortex (mPFC) glutamate mediates sexual behavior activation of the nucleus accumbens. Glutamatergic neurons in the mPFC were activated by sex behavior, and these sex-activated cells shown to project to the nucleus accumbens. During sexual interactions with the male, glutamate transients recorded in the nucleus accumbens of female hamsters were specifically associated with the receipt of intromissions from the male. Further, inhibition of the mPFC during sex significantly decreased nucleus accumbens activation. Glutamatergic medial prefrontal cortical input to the nucleus accumbens mediates the activity in the nucleus accumbens during female sexual behavior. These results offer novel insights into the neurobiology of the motivational control of female sexual behavior and provide attractive avenues for pursuing target-specific and clinically-relevant therapies for sexual dysfunction in women.