下丘脑室旁核中mu型阿片受体通过中枢交感神经调控大鼠射精行为

Mu-opioid receptors in the paraventricular nucleus regulate ejaculatory behaviors via the sympathetic nerve system in male rats

目的:探究下丘脑室旁核(PVN)中mu型阿片受体(MOR)对大鼠射精行为的影响及其内在机制。方法:选取具有射精行为的雄性SD大鼠与激素诱导的发情期雌性SD大鼠进行交配实验,双侧PVN置管给予MOR激动剂DAGO或拮抗剂CTAP,观察并比较雄鼠性行为变化情况。此外,选取雄性SD大鼠,采用立体定位仪进行双侧PVN核团微量注射,分别给予saline,不同浓度的DAGO以及CTAP,利用Powerlab生物信号采集系统记录腰交感神经(LSNA)放电的变化情况,同时利用酶联免疫吸附实验(ELISA)测定外周血浆中去甲肾上腺素(NE)水平变化情况。结果:DAGO和CTAP对雄鼠的骑跨潜伏期(ML)无明显影响(P>0.05)。但是,DGAO可明显增加雄鼠的插入次数(IF)和骑跨次数(MF)(P均<0.01),同时延长插入潜伏期(IL),射精潜伏期(EL)和射精后间隔期(PEI)(P均<0.01),并且减少射精次数(EF)(P<0.01),降低插入比例(IR)(P<0.05);相反,CTAP则可显著减少雄鼠的IF和MF(P均<0.01),缩短IL,EL和PEI(P均<0.01),同时增加EF(P<0.01),提高IR(P<0.01)。此外,DAGO能够降低LSNA,且呈剂量依赖性,降低血浆NE水平;而CTAP不仅可抵消DAGO对LSNA的减弱作用,还能显著增强LSNA。结论:PVN中MOR对雄性大鼠的射精行为有抑制作用,可能与其降低交感神经的兴奋性有关,有望为临床应用高选择性阿片类药物治疗早泄提供理论依据。

Objective: To explore the effects of the mu-opioid receptor(MOR) in the paraventricular nucleus(PVN) on the ejaculatory behaviors of male rats and its potential mechanisms. Methods: Male SD rats with normal ejaculation ability were mated with female ones in hormone-induced estrus. After bilateral PVN microinjection of D-Ala-2-Me-Phe-4-Gly-ol enkephalin(DAGO) or D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2(CTAP) with an inserted catheter, the male animals were observed for mount latency(ML), mount frequency(MF), intromission latency(IL), intromission frequency(IF), ejaculation latency(EL), ejaculation frequency(EF), post-ejaculation interval(PEI), and intromission ratio(IR). The lumbar sympathetic nerve activity(LSNA) of the rats was recorded using the PowerLab data acquisition hardware device, and the levels of norepinephrine(NE) in the peripheral plasma were measured by ELISA following microinjection of saline or different doses of DAGO or CTAP. Results: Neither CTAP nor DGAO significantly affected the ML of the male rats(P > 0.05). DGAO remarkably increased IF(P < 0.01) and MF(P < 0.01), prolonged IL(P < 0.01), EL(P < 0.01) and PEI(P < 0.01), and reduced EF(P <0.01) and IR(P < 0.05). On the contrary, CTAP markedly decreased IF(P < 0.01) and MF(P < 0.01), shortened IL(P < 0.01), EL(P < 0.01) and PFI(P < 0.01), and elevated EF(P < 0.01) and IR(P < 0.01). Additionally, DAGO decreased LSNA in a dose-dependent manner and reduced the NE level in the peripheral plasma. CTAP, however, not only offset the effects of DAGO on LSNA, but also significantly increased LSNA. Conclusion: MOR in PVN inhibits ejaculatory behaviors in male rats by weakening LSNA, which has provided some theoretical evidence for the use of highly selective opioids in the treatment of premature ejaculation. Natl J Androl, 2020, 26(10): 867-874.