Abstract
Estrogen and progesterone (P4) act in neural circuits to elicit lordosis, the stereotypical female sexual receptivity behavior. Estradiol acts through membrane receptors to rapidly activate a limbic-hypothalamic circuit consisting of the arcuate (ARH), medial preoptic (MPN), and ventromedial (VMH) nuclei of the hypothalamus. This initial activation results in a transient but necessary inhibition of lordosis, which appears to be a result of the release of β-endorphin (β-End) from proopiomelanocortin (POMC) terminals onto cells containing the µ-opioid receptor (MOR) in the MPN. To functionally examine the role of the MOR in the hypothalamic lordosis circuit, we transfected a channelrhodopsin (ChR2) adeno-associated virus into POMC cell bodies in the ARH and photostimulated POMC/β-End axon terminals in the MPN in sexually receptive female Pomc-cre mice. Following estrogen and P4 priming, sexual receptivity was assessed by measuring the lordosis quotient (LQ). Following an initial trial for sexual receptivity, mice were photostimulated during behavioral testing, and brains were processed for MOR immunohistochemistry (IHC). Photostimulation decreased the LQ only in ChR2-expressing Pomc-cre mice. Furthermore, photostimulation of ChR2 in POMC/β-End axon terminals in the MPN resulted in the internalization of MOR, indicating activation of the receptor. Our results suggest that the activation of the MOR in the MPN is sufficient to attenuate lordosis behavior in a hormone-primed, sexually receptive female mouse. These data support a central role of MOR in female sexual behavior, and provide further insight into the hypothalamus control of sexual receptivity.