Hypothalamic neuropeptide signaling in alcohol addiction.
Hypothalamic neuropeptide signaling in alcohol addiction.
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DOI：
10.1016/j.pnpbp.2015.02.006
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发表时间：
2016-02-04
影响因子：
5.6
通讯作者：
Leibowitz SF
中科院分区：
文献类型：
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作者：
Barson JR;Leibowitz SF
现在已知下丘脑除了在食物摄入中的既定作用之外还调节酒精摄入，部分是通过称为神经肽的神经调节神经化学物质。某些食欲神经肽在下丘脑中起作用以促进饮酒，尽管它们影响饮酒反应的不同方面。这些神经肽，包括甘丙肽，内源性阿片类脑啡肽和食欲素/下丘脑泌素，似乎刺激酒精摄入不仅通过促进食物摄入的机制，而且还通过增强奖励和酒精强化。此外，这些神经肽参与与酒精的正反馈关系，因此它们被酒精摄入量上调，以促进进一步的消费。它们与其他促食欲神经肽（如黑色素浓缩激素和神经肽Y）形成对比，后者在有限的情况下促进酒精摄入，并不总是受到酒精的刺激，也不会增强奖励。它们也与可促食欲的神经肽形成对比，包括内源性阿片类强啡肽、促肾上腺皮质激素释放因子和黑皮质素，其在下丘脑中起作用以抑制饮酒以及奖励，因此对抗由促食欲神经肽促进的摄食驱动。因此，虽然多个下丘脑神经肽可以一起调节饮酒反应的不同方面，但来自食欲神经肽的过度信号传导或来自食欲神经肽的信号传导不足可以因此允许饮酒变得失调。
The hypothalamus is now known to regulate alcohol intake in addition to its established role in food intake, in part through neuromodulatory neurochemicals termed neuropeptides. Certain orexigenic neuropeptides act in the hypothalamus to promote alcohol drinking, although they affect different aspects of the drinking response. These neuropeptides, which include galanin, the endogenous opioid enkephalin, and orexin/hypocretin, appear to stimulate alcohol intake not only through mechanisms that promote food intake but also by enhancing reward and reinforcement from alcohol. Moreover, these neuropeptides participate in a positive feedback relationship with alcohol, whereby they are upregulated by alcohol intake to promote even further consumption. They contrast with other orexigenic neuropeptides, such as melanin-concentrating hormone and neuropeptide Y, which promote alcohol intake under limited circumstances, are not consistently stimulated by alcohol, and do not enhance reward. They also contrast with neuropeptides that can be anorexigenic, including the endogenous opioid dynorphin, corticotropin-releasing factor, and melanocortins, which act in the hypothalamus to inhibit alcohol drinking as well as reward and therefore counter the ingestive drive promoted by orexigenic neuropeptides. Thus, while multiple hypothalamic neuropeptides may work together to regulate different aspects of the alcohol drinking response, excessive signaling from orexigenic neuropeptides or inadequate signaling from anorexigenic neuropeptides can therefore allow alcohol drinking to become dysregulated.