Activation of μ opioid receptors in the medial preoptic area following copulation in male rats

The current study tested the hypothesis that sexual behavior is a biological stimulus for release of endogenous opioid peptides. In particular, activation of μ opioid receptors (MOR) in the medial preoptic area (MPOA), a key area for regulation of male sexual behavior, was studied in male rats. MOR endocytosis or internalization was used as a marker for ligand-induced receptor activation, utilizing confocal, electron, and bright microscopic analysis. Indeed, mating including one ejaculation induced receptor activation in the MPOA, demonstrated by increased immunoreactivity for MOR, increased numbers of endosome-like particles immunoreactive for MOR inside the cytoplasm of neurons, and increased percentage of neurons with three or more endosome-like particles inside the cytosol. Moreover, it was demonstrated that MOR activation occurred within 30 min following mating and was still evident after 6 h. Mating-induced internalization was prevented by treatment with the opioid receptor antagonist naloxone before mating, suggesting that mating-induced receptor activation is a result of action of endogenous MOR ligands. I.c.v. injections of MOR ligand [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin resulted in internalization of the MOR in a similar manner observed following mating. Finally, mating induced Fos expression in MOR containing neurons in the MPOA. However, naloxone pretreatment did not prevent Fos activation of MOR neurons, suggesting that Fos induction was not the result of MOR activation. In summary, these results provide further evidence that endogenous opioid peptides are released in the MPOA during male sexual behavior.