Neuropeptide Y signaling in the dorsal raphe nucleus inhibits male sexual behavior in mice

- Male sexual behavior is inhibited under a low energy condition.
- NPY-positive neuronal processes are distributed in the dorsal raphe nucleus.
- The Y1 receptor is expressed in serotonergic neurons of the dorsal raphe nucleus.
- NPY inhibits male sexual behavior via the Y1 receptor in the dorsal raphe nucleus.

Animals change their biological activities depending on their nutritional state. Reproductive functions, including sexual behavior, are suppressed under low-energy conditions; however, the underlying neuronal mechanism is poorly understood. Neuropeptide Y (NPY) is an orexigenic molecule released in response to low-energy conditions and has an inhibitory effect on sexual behavior. We examined how NPY is involved in energy state-dependent regulation of male sexual behavior. Mounting, intromission, and ejaculation were evaluated as parameters of sexual behavior. Almost all parameters indicated that fasting for 24 h suppressed male sexual behavior. Intracerebroventricular injection of NPY inhibited sexual behavior in males that free-fed for 8 h following 24-h fasting (fed males). We next examined whether the dorsal raphe nucleus (DRN), in which serotonergic (5-HT) neurons are distributed, is involved in NPY-mediated inhibition of male sexual behavior. NPY-positive processes immunoreactive for a presynaptic marker, synaptophysin, were distributed in the DRN of both fed and fasted males. Expression of the NPY Y1 receptor in 5-HT neurons was also observed. Direct injection of NPY or 8-OH-DPAT (a 5-HT1A receptor agonist that inhibits the activity of 5-HT neurons) into the DRN inhibited male sexual behavior in fed males. In contrast, injection of BIBP-3226, a NPY Y1 receptor antagonist, or (+)-DOI hydrochloride (DOI), a 5-HT2A/2C receptor agonist that activates 5-HT neurons, into the DRN partially recovered male sexual behavior in 24-h fasted males. These results suggest that NPY inhibits serotonergic neuronal activity via the Y1 receptor in the DRN, resulting in suppression of male sexual behavior in low-energy conditions.