Presynaptic actions of opioid receptor agonists in ventromedial hypothalamic neurons in estrogen- and oil-treated female mice.
Presynaptic actions of opioid receptor agonists in ventromedial hypothalamic neurons in estrogen- and oil-treated female mice.
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阿片受体激动剂在雌激素和油处理的雌性小鼠腹内侧下丘脑神经元中的突触前作用。
DOI：
10.1016/j.neuroscience.2008.01.033
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发表时间：
2008
期刊：
影响因子：
3.3
通讯作者：
Pfaff,DW
中科院分区：
文献类型：
--
作者：
Devidze,N;Zhang,Q;Zhou,J;Lee,AW;Pataky,S;Kow,L-M;Pfaff,DW
雌激素作用于下丘脑腹内侧核（VMH）神经元，其对女性唤醒和性行为的影响涉及多种神经递质和神经调质。其中阿片肽可能被预测为对抗雌激素对VMH的作用，因为它们倾向于降低CNS唤醒。用全细胞膜片钳技术记录了17只β-雌二醇（10 μg/0.1ml）或油处理的对照去卵巢（OVX）小鼠VMH神经元自发兴奋性突触后电流。为了检查阿片类药物输入的影响，在存在一般阿片受体激动剂甲硫氨酸脑啡肽-Arg-Phe（MERF，3 μM）或μ-受体特异性激动剂[d-Ala 2，N-Me-Phe 4，Gly 5-ol]-脑啡肽（DAMGO，1 μM）的情况下，记录了两个给药组的神经元。与油相比，E处理48 h显著增加自发兴奋性突触后电流（sEPSC）的频率，而不影响其幅度。MERF和DAMGO各自消除了这种E效应，导致sEPSC显着减少。纳洛酮可阻断MERF的作用（一般阿片受体拮抗剂，3 μM）和DAMGO通过d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH 2（CTAP）的作用（μ-阿片受体选择性拮抗剂，1 μM）;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，1 μM）与DAMGO相比，对sEPSCs的影响很小。为了考虑阿片类药物的突触前与突触后效应，在E和油处理的VMH神经元中研究了微型兴奋性突触后电流（mEPSC），并观察了阿片受体拮抗剂对mEPSC的作用。MERF和DAMGO均降低mEPSC的频率，但对其振幅无影响。我们的研究结果表明，阿片类药物主要通过μ受体抑制VMH神经元的兴奋性突触传递，从而降低小鼠的性唤起。
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 17β-estradiol- (E, 10 μg/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 μM), or μ-receptor specific agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO, 1 μM). 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 μM) and the effect of DAMGO by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(CTAP) (μ-opioid receptor selective antagonist, 1 μM); in contrast, κ- and δ-opioid receptor agonists, U69593 (300 nM) and [d-Pen2,d-Pen5]-enkephalin (DPDPE, 1 μM) 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 μ-receptors and could thereby decrease sexual arousal in mice.