Addiction and arousal: The hypocretin connection
Addiction and arousal: The hypocretin connection
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DOI：
10.1016/j.physbeh.2007.11.022
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发表时间：
2008-03-18
影响因子：
2.9
通讯作者：
de Lecea, Luis
中科院分区：
文献类型：
--
作者：
Boutrel, Benjamin;de Lecea, Luis
下丘脑泌素，也称为食欲素，是两种神经肽，现在通常被描述为维持和调节唤醒稳定性的关键成分。有几条证据提出了一个假设，即产生下视丘分泌素的神经元是介导下丘脑对急性应激反应的回路的一部分。下丘脑泌素脑内给药导致药物和食物寻求行为的剂量相关性恢复。此外，应激诱导的恢复可以用下丘脑泌素受体I拮抗剂阻断。这些结果，再加上最近的数据显示，下丘脑泌素是至关重要的参与可卡因敏化通过招募NMDA受体在腹侧被盖区，强烈表明，下丘脑泌素神经元的激活在成瘾过程的发展中起着至关重要的作用。下丘脑泌素神经元的活动可能通过促进大脑敏化或调节大脑奖赏系统来影响成瘾行为。下丘脑泌素能细胞与大脑应激系统协调可能导致易受伤害的状态，从而促进药物寻求行为的恢复。因此，下丘脑泌素能系统是一个新的药物靶点，可用于预防药物寻求复发。(C)2007年爱思唯尔公司All rights reserved.
The hypocretins, also known as orexins, are two neuropeptides now commonly described as critical components to maintain and regulate the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. Intracerebral administration of hypocretin leads to a dose-related reinstatement of drug and food seeking behaviors. Furthermore, stress-induced reinstatement can be blocked with hypocretin receptor I antagonism. These results, together with recent data showing that hypocretin is critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area, strongly suggest that activation of hypocretin neurons play a critical role in the development of the addiction process. The activity of hypocretin neurons may affect addictive behavior by contributing to brain sensitization or by modulating the brain reward system. Hypocretinergic cells, in coordination with brain stress systems may lead to a vulnerable state that facilitates the resumption of drug seeking behavior. Hence, the hypocretinergic system is a new drug target that may be used to prevent relapse of drug seeking. (C) 2007 Elsevier Inc. All rights reserved.