Hood Lauren E, Nagy Erin K, Leyrer-Jackson Jonna M, Olive M Foster
Department of Psychology, Arizona State University, Tempe, Arizona, 85281, USA.
Physiol Rep. 2022 Mar;10(6):e15231. doi: 10.14814/phy2.15231.
Ethanol activates various opioid peptide-containing circuits within the brain that may underlie its motivational and rewarding effects. One component of this circuitry consists of neurons located in the arcuate nucleus (ArcN) of the hypothalamus which express pro-opiomelanocortin (POMC), an opioid precursor peptide that is cleaved to form bioactive fragments including β-endorphin and α-melanocyte stimulating hormone. In this study, we sought to determine if ethanol intake activates ArcN POMC neurons as measured by expression of the immediate early gene c-fos. Male and female POMC-EGFP mice underwent drinking-in-the-dark (DID) procedures for 3 consecutive days (2 h/day) and were allowed to consume either ethanol (20% v/v), saccharin (0.2% w/v), or water. On the fourth day of DID procedures, animals were allowed to consume their respective solutions for 20 min, and 1 h following the session brains were harvested and processed for c-fos immunohistochemistry and co-localization with EGFP. Our results indicate that ethanol intake activates a subset (15-20%) of ArcN POMC neurons, whereas saccharin or water intake activates significantly fewer (5-12%) of these neurons. The percent of activated POMC neurons did not correlate with blood ethanol levels at the time of tissue collection, and activation appeared to be distributed throughout the rostrocaudal axis of the ArcN. No sex differences were observed in the degree of neuronal activation across drinking solutions. These findings indicate a preferential activation of ArcN POMC neurons by ethanol consumption, strengthening the notion that ethanol activates endogenous opioid systems in the brain which may underlie its motivational properties.
乙醇激活大脑内各种含有阿片肽的神经回路，这可能是其产生动机和奖赏效应的基础。该神经回路的一个组成部分是位于下丘脑弓状核（ArcN）的神经元，这些神经元表达阿片促黑皮质素原（POMC），这是一种阿片前体肽，可被切割形成包括β-内啡肽和α-黑素细胞刺激素在内的生物活性片段。在本研究中，我们试图确定乙醇摄入是否会通过立即早期基因c-fos的表达来激活ArcN POMC神经元。雄性和雌性POMC-EGFP小鼠连续3天（每天2小时）进行黑暗中饮水（DID）实验，并允许它们饮用乙醇（20% v/v）、糖精（0.2% w/v）或水。在DID实验的第四天，让动物饮用各自的溶液20分钟，实验结束1小时后，采集大脑并进行处理，用于c-fos免疫组织化学分析以及与EGFP的共定位分析。我们的结果表明，乙醇摄入会激活ArcN POMC神经元的一个子集（约15-20%），而糖精或水的摄入激活的这类神经元明显较少（约5-12%）。激活的POMC神经元百分比与组织采集时的血液乙醇水平无关，且激活似乎分布在ArcN的整个前后轴上。在不同饮用溶液条件下，未观察到神经元激活程度的性别差异。这些发现表明，乙醇摄入会优先激活ArcN POMC神经元，强化了乙醇激活大脑内源性阿片系统这一观点，而这可能是其具有动机性质的基础。
