β-Endorphin and sex differentially modulate the response to EtOH in a site-specific manner.
β-Endorphin and sex differentially modulate the response to EtOH in a site-specific manner.
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β-内啡肽和性别以位点特异性方式差异调节对 EtOH 的反应。
DOI：
10.1016/j.brainres.2020.146845
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Grisel,JudithE
中科院分区：
文献类型：
--
作者：
Rhinehart,ErinM;Waldron,Madison;Kelly-Quigley,Hannah;Zellers,McKenzie;Turco,Abby;Grisel,JudithE
酒精的影响是多方面的，涉及调节奖励、动机和压力的大脑回路，通常是通过内源性阿片类物质-内啡肽（β-E）产生的。目前尚不清楚酒精如何影响女性神经回路的激活，以及β-E如何影响乙醇诱导神经元激活的能力。因此，我们以性别和β-E依赖的方式研究了急性酒精治疗对奖励和压力相关脑回路中神经元激活的影响。在本研究中，雄性和雌性对照（C57BL/6J; β-E+/+）和β-E null（−/−）小鼠腹腔注射2g /kg乙醇（EtOH）或生理盐水。注射后，用氯胺酮/噻嗪处死动物，用生理盐水灌注4%多聚甲醛。对35 μm脑切片进行免疫组织化学处理，检测酪氨酸羟化酶（TH）、多巴胺限速酶和神经元激活标志物c-fos。测定伏隔核（NAc）、腹侧被盖区（VTA）、室旁核（PVN）、杏仁核中央核（CeA）、室旁丘脑核（PVA）和Edinger-Westphal核（EW）中c-fos免疫反应细胞核的数量、TH免疫反应性和TH/c-fos-ir细胞的数量。在女性中，EtOH增加了CeA、PVN、EW和NAc外壳中c-fos的表达，而VTA中c-fos的表达以及VTA和NAc中TH的表达取决于基因型和治疗的相互作用。在男性中，EtOH增加了CeA和PVN的c-fos。EtOH也增加了Arc中双标记细胞的数量，但仅在女性中。这些结果表明，女性的神经元天生对EtOH更敏感，强调了研究性与酒精成瘾之间关系的重要性。
The effects of alcohol are multifaceted, involving brain circuits regulating reward, motivation, and stress, frequently via the endogenous opioid, beta-endorphin (β-E). It is currently unknown how alcohol affects neural circuit activation in females and how β-E affects ethanol's ability to induce neuronal activation. Therefore, we investigated the impact of acute alcohol treatment on neuronal activation in reward- and stress-related brain circuitry in a sex- and β-E dependent manner. In this study, male and female control (C57BL/6J; β-E+/+) and β-E null (−/−) mice were injected intraperitoneally with 2 g/kg ethanol (EtOH) or saline. Post-injection, animals were sacrificed using ketamine/xylazine and perfused with saline followed by 4% paraformaldehyde. Brain sections (35 μm) were immunohistochemically processed for tyrosine hydroxylase (TH), dopamine's rate-limiting enzyme, and c-fos, a neuronal activation marker. The number of c-fos immunoreactive cell nuclei, TH-immunoreactivity, and TH/c-fos-ir cells were quantified in the nucleus accumbens (NAc), ventral tegmental area (VTA), paraventricular nucleus (PVN), central nucleus of the amygdala (CeA), paraventricular thalamic nucleus (PVA) and Edinger-Westphal nucleus (EW). In females, EtOH increased c-fos expression in the CeA, PVN, EW and NAc shell, while c-fos expression in the VTA, and TH expression in the VTA and NAc, depended on a genotype and treatment interaction. In males, EtOH increased c-fos in the CeA and PVN. EtOH also increased the number of double-labeled cells in the Arc, but only in females. These results suggest that the neurons in females are inherently more sensitive to EtOH, emphasizing the importance of studying the relationship between sex and alcohol addiction.