Summary of the principal findings.

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.

成年大脑的神经发生主要发生在海马齿状回（dentate gyrus of the hippocampus, DG）与嗅球（olfactory bulbs），新生细胞从室管膜下区迁移而来。此外，在视前区（preoptic area, POA）和杏仁核（amygdala, AMG）——这两个区域参与调控雄性性行为——中也观察到少量细胞增殖现象。性行为可诱导由阿片类物质介导的奖赏状态，本团队此前已证实，雌性大鼠的可控交配（paced mating）所诱导的神经发生依赖阿片信号通路。因此，本研究旨在探究盐酸纳洛酮能否阻断雄性大鼠交配行为诱导的细胞增殖与神经发生。我们对6组雄性大鼠的海马齿状回、主嗅球（main olfactory bulb, MOB）、副嗅球（accessory olfactory bulb, AOB）、视前区以及杏仁核的细胞增殖与神经发生水平进行了评估：6组分别为未发生性接触且注射生理盐水或纳洛酮的大鼠、交配至射精1次且注射生理盐水或纳洛酮的大鼠，以及交配至射精3次且注射生理盐水或纳洛酮的大鼠。研究结果显示，在副嗅球与主嗅球的肾小球层中，3次射精后观察到的细胞增殖与神经发生水平升高可通过纳洛酮给药完全消除；该效应同样见于主嗅球的颗粒层。与之相反，纳洛酮并未降低副嗅球颗粒层中3次射精诱导的细胞增殖，但显著抑制了该区域的神经发生。在海马齿状回中，3次射精可提升细胞增殖与神经发生水平，而纳洛酮可阻断这一效应。最后，对视前区与杏仁核的分析表明，纳洛酮可阻断3次射精诱导的细胞增殖。本研究证实了阿片信号通路在介导性行为对经典与非经典神经发生区域的细胞增殖及神经发生的调控作用中发挥核心作用。