Devidze N, Zhang Q, Zhou J, Lee A W, Pataky S, Kow L-M, Pfaff D W
Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Neuroscience. 2008 Apr 9;152(4):942-9. doi: 10.1016/j.neuroscience.2008.01.033. Epub 2008 Feb 5.
Estrogens act upon ventromedial hypothalamic (VMH) neurons, and their effects on female arousal and sexual behaviors mediated by VMH neurons involve several neurotransmitters and neuromodulators. Among these are opioid peptides which might be predicted to oppose estrogenic action on VMH because they tend to decrease CNS arousal. Spontaneous excitatory postsynaptic currents were recorded from VMH neurons from 17beta-estradiol- (E, 10 mug/0.1 ml) or oil-treated control ovariectomized (OVX) mice using whole-cell patch-clamp techniques. To examine the impact of opioidergic inputs, recordings of neurons from both treatment groups were obtained in the presence of the general opioid receptor agonist methionine enkephalin-Arg-Phe (MERF, 3 muM), or mu-receptor specific agonist [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO, 1 muM). Compared with oil, E treatment for 48 h significantly increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) without affecting their amplitude. MERF and DAMGO each abolished this E effect, causing significant reductions in sEPSCs. The effect of MERF was abolished by naltrexone (general opioid receptor antagonist, 3 muM) and the effect of DAMGO by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) (mu-opioid receptor selective antagonist, 1 muM); in contrast, kappa- and delta-opioid receptor agonists, U69593 (300 nM) and [d-Pen(2),d-Pen(5)]-enkephalin (DPDPE, 1 muM) respectively, had little effect on the sEPSCs compared with DAMGO. To consider presynaptic vs. postsynaptic effects of opioids, miniature excitatory postsynaptic currents (mEPSCs) were investigated in E- and oil-treated VMH neurons and opioid receptor antagonist effects on mEPSCs were observed. Both MERF and DAMGO reduced the frequency of mEPSCs, but had no effect on their amplitude. Our findings indicate that opioids suppress excitatory synaptic transmissions in VMH neurons primarily through mu-receptors and could thereby decrease sexual arousal in mice.
雌激素作用于下丘脑腹内侧核（VMH）神经元，其通过VMH神经元对雌性唤起和性行为的影响涉及多种神经递质和神经调质。其中包括阿片肽，由于它们往往会降低中枢神经系统的唤起，因此可能会对抗雌激素对VMH的作用。使用全细胞膜片钳技术，记录了来自17β-雌二醇（E，10μg/0.1ml）或油处理的对照去卵巢（OVX）小鼠的VMH神经元的自发性兴奋性突触后电流。为了研究阿片能输入的影响，在一般阿片受体激动剂甲硫氨酸脑啡肽-Arg-Phe（MERF，3μM）或μ受体特异性激动剂[d-Ala(2)，N-Me-Phe(4)，Gly(5)-ol]-脑啡肽（DAMGO，1μM）存在的情况下，获得了两个治疗组神经元的记录。与油相比，E处理48小时显著增加了自发性兴奋性突触后电流（sEPSCs）的频率，而不影响其幅度。MERF和DAMGO均消除了这种E效应，导致sEPSCs显著减少。纳曲酮（一般阿片受体拮抗剂，3μM）消除了MERF的作用，而d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH₂（CTAP）（μ阿片受体选择性拮抗剂，1μM）消除了DAMGO的作用；相反，κ和δ阿片受体激动剂U69593（300 nM）和[d-Pen(2)，d-Pen(5)]-脑啡肽（DPDPE，1μM）与DAMGO相比，对sEPSCs几乎没有影响。为了考虑阿片类药物的突触前与突触后效应，研究了E处理和油处理的VMH神经元中的微小兴奋性突触后电流（mEPSCs），并观察了阿片受体拮抗剂对mEPSCs的影响。MERF和DAMGO均降低了mEPSCs的频率，但对其幅度没有影响。我们的研究结果表明，阿片类药物主要通过μ受体抑制VMH神经元中的兴奋性突触传递，从而可能降低小鼠的性唤起。
