A role for lateral hypothalamic orexin neurons in reward seeking
A role for lateral hypothalamic orexin neurons in reward seeking
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DOI：
10.1038/nature04071
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发表时间：
2005-09-22
期刊：
影响因子：
64.8
通讯作者：
Aston-Jones, G
中科院分区：
文献类型：
--
作者：
Harris, GC;Wimmer, M;Aston-Jones, G
外侧下丘脑是一个大脑区域，历史上与奖励和动机有关(1-4)，但参与其中的神经递质的身份尚不清楚。食欲素是最近在下丘脑外侧神经元中被确认为神经递质的神经肽(5，6)。虽然基因敲除和转基因过表达研究表明，食欲素神经元与觉醒和睡眠有关(7)，但这些细胞也投射到与奖赏相关的大脑区域，包括伏隔核和腹侧被盖区(8，9)。这表明这些神经元可能在奖赏功能和动机中发挥作用(3，10)，这与先前关于这些神经元与进食有关的研究一致(6)。在这里，我们表明，激活外侧下丘脑的食欲素神经元与对与药物和食物奖励相关的线索的偏好有很强的联系。此外，我们还表明，化学激活下丘脑外侧增食欲素神经元可以恢复已熄灭的寻药行为。这种恢复作用可被预先给予食欲素A拮抗剂完全阻断。此外，将食欲素A多肽直接注入腹侧被盖区也恢复了药物寻找。这些数据揭示了下丘脑外侧增食欲素神经元在奖赏寻求、药物复发和成瘾中的新角色。
The lateral hypothalamus is a brain region historically implicated in reward and motivation(1 - 4), but the identity of the neurotransmitters involved are unknown. The orexins ( or hypocretins) are neuropeptides recently identified as neurotransmitters in lateral hypothalamus neurons(5,6). Although knockout and transgenic overexpression studies have implicated orexin neurons in arousal and sleep(7), these cells also project to reward- associated brain regions, including the nucleus accumbens and ventral tegmental area(8,9). This indicates a possible role for these neurons in reward function and motivation(3,10), consistent with previous studies implicating these neurons in feeding(6). Here we show that activation of lateral hypothalamus orexin neurons is strongly linked to preferences for cues associated with drug and food reward. In addition, we show that chemical activation of lateral hypothalamus orexin neurons reinstates an extinguished drug- seeking behaviour. This reinstatement effect was completely blocked by prior administration of an orexin A antagonist. Moreover, administration of the orexin A peptide directly into the ventral tegmental area also reinstated drug- seeking. These data reveal a new role for lateral hypothalamus orexin neurons in reward- seeking, drug relapse and addiction.