Alcohol consumption preferentially activates a subset of pro-opiomelanocortin (POMC) producing neurons targeting the amygdala.
Alcohol consumption preferentially activates a subset of pro-opiomelanocortin (POMC) producing neurons targeting the amygdala.
复制标题
酒精消耗优先激活一个子集的前阿黑皮素（POMC）生产神经元靶向杏仁核。
DOI：
10.1016/j.neuropharm.2021.108674
复制
发表时间：
2021-09-01
影响因子：
4.7
通讯作者：
Olive MF
中科院分区：
文献类型：
--
作者：
Leyrer-Jackson JM;Hood LE;Olive MF
酒精滥用是一个全球性的公共卫生问题，在美国每年估计有90，000例与酒精有关的死亡。酒精可能会促进其欣快和动机的影响，部分，通过激活内源性阿片系统。位于下丘脑弓状核（ArcN）内的产生前阿黑皮素（POMC）的神经元构成内源性阿片系统的一个回路，并且大量投射到与奖赏相关的脑区，如杏仁核（amygdala）、中脑核（NAc）和腹侧被盖区（VTA）。产生POMC的神经元释放β-内啡肽和其他肽，这些肽靶向奖赏区内的阿片受体，以引起相关的奖赏效应。在这里，我们探讨了ArcN POMC神经元激活，通过FosB表达评估，饮酒后，以确定激活是否不同的ArcN POMC投射神经元的子集，针对不同的奖励相关领域。使用荧光逆转录珠标记表达报告基因tdTomato的POMC-cre小鼠中靶向NAc、杏仁核和VTA的ArcN POMC投射神经元。然后允许动物（n=49）使用在黑暗中饮酒（DID）范例自愿饮酒，并处死用于免疫组织化学以检查ArcN POMC神经元内的FosB表达。雌性小鼠在DID期间显示酒精摄入量的增加，而雄性小鼠则没有。更大比例的ArcN POMC神经元靶向杏仁核，而不是NAc和VTA，酒精消耗优先激活针对杏仁核的ArcN POMC神经元。这些研究结果突出了一个新的方面酒精诱导的内源性阿片系统的激活，酒精激活特定的亚群的ArcN POMC生产神经元，主要项目的杏仁核。
Alcohol abuse is a worldwide public health concern and leads to an estimated 90,000 alcohol-related deaths in the United States annually. Alcohol may promote its euphoric and motivational effects, in part, by activating the endogenous opioid system. Pro-opiomelanocortin (POMC) producing neurons located within the arcuate nucleus (ArcN) of the hypothalamus make up one circuit of the endogenous opioid system, and heavily projects to reward-related brain areas such as the amygdala, nucleus accumbens (NAc) and ventral tegmental area (VTA). POMC producing neurons release β-endorphin and other peptides that target opioid receptors within reward areas to elicit the associated rewarding effects. Here we explore ArcN POMC neuronal activation, as assessed via FosB expression, following alcohol consumption to determine whether activation varied within subsets of ArcN POMC projection neurons targeting different reward-related areas. Fluorescent retrobeads were used to label ArcN POMC projection neurons targeting the NAc, amygdala and VTA in POMC-cre mice expressing the reporter tdTomato. Animals (n=49) were then allowed to voluntarily consume alcohol using the drinking-in-the-dark (DID) paradigm, and sacrificed for immunohistochemistry to examine FosB expression within ArcN POMC neurons. Female mice displayed escalation of alcohol intake across DID sessions, whereas males did not. A greater percent of ArcN POMC neurons target the amygdala over the NAc and VTA, and alcohol consumption preferentially activated ArcN POMC neurons targeting the amygdala over other areas. These findings highlight a novel aspect alcohol-induced activation of the endogenous opioid system, whereby alcohol activates a specific subpopulation of ArcN POMC producing neurons that project primarily to the amygdala.
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DOI：
10.1111/febs.15496
发表时间：
2021-03
期刊：
The FEBS journal
影响因子：
--
作者：
Buck SA;Torregrossa MM;Logan RW;Freyberg Z
通讯作者：
Freyberg Z
影响因子：
5
作者：
BALSKUBIK, R;SHIPPENBERG, TS;HERZ, A
通讯作者：
HERZ, A
影响因子：
2.3
作者：
Gianoulakis, C;DeWaele, JP;Thavundayil, J
通讯作者：
Thavundayil, J
影响因子：
3.6
作者：
Becker, A;Grecksch, G;Höllt, V
通讯作者：
Höllt, V
影响因子：
64.8
作者：
BELLUZZI, JD;STEIN, L
通讯作者：
STEIN, L