Mating-induced neurogenesis and cell proliferation in male rats depend on opioid signaling

In the adult brain, neurogenesis primarily occurs in the dentate gyrus of the hippocampus (DG) and the olfactory bulbs, with new cells migrating from the subventricular zone. Additionally, small amounts of cell proliferation have been observed in the preoptic area (POA) and the amygdala (AMG), regions involved in the control of male sexual behavior. Sexual activity induces a reward state mediated by opioids, and our group previously demonstrated that neurogenesis induced by paced mating is opioid dependent in female rats. Therefore, in the present study, we examined whether naloxone hydrochloride could block the cell proliferation and neurogenesis induced by mating in male rats. We evaluated cell proliferation and neurogenesis in the DG, main (MOB) and accessory (AOB) olfactory bulbs, POA and AMG across 6 groups of male rats: without sexual contact injected with saline or NX, males that mated until they ejaculated once injected with saline or NX and males that mated until they ejaculated 3 times injected with saline or NX. Our findings indicated that the increase of cell proliferation and neurogenesis observed after 3 ejaculations was abolished by NX administration in the glomerular layer of both the AOB and MOB. The same effect was observed in the granular layer of the MOB. In contrast, NX did not reduce the cell proliferation induced by 3 ejaculations in the granular layer of the AOB, but significantly reduced neurogenesis. In the DG, cell proliferation and neurogenesis were increased by 3 ejaculations and NX blocked this effect. Finally, analyses of the AMG and POA revealed that NX blocked the cell proliferation induced by 3 ejaculations. This study highlights the central role of opioid signaling in mediating the effects of sexual behavior on cell proliferation and neurogenesis in both classical and non-classical neurogenic regions.