Regulation of dopaminergic transmission and cocaine reward by the Clock gene
Regulation of dopaminergic transmission and cocaine reward by the Clock gene
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DOI：
10.1073/pnas.0503584102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Nestler, EJ
中科院分区：
文献类型：
--
作者：
McClung, CA;Sidiropoulou, K;Nestler, EJ
虽然昼夜节律和药物成瘾之间存在明显的相互作用，但这种相互作用的机制仍然未知。在这里，我们确定了时钟基因在调节大脑奖励回路中的作用。缺乏功能性Clock基因的小鼠表现出可卡因奖励和中脑腹侧被盖区多巴胺神经元兴奋性的增加，这是一个关键的大脑奖励区域。这些表型与酪氨酸羟化酶（多巴胺合成的限速酶）的表达和磷酸化增加以及已知调节腹侧被盖区多巴胺活性的几个基因的变化有关。这些发现证明了昼夜节律相关基因Clock参与调节多巴胺功能和可卡因奖励。
Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Here we establish a role for the Clock gene in regulating the brain's reward circuit. Mice lacking a functional Clock gene display an increase in cocaine reward and in the excitability of dopamine neurons in the midbrain ventral tegmental area, a key brain reward region. These phenotypes are associated with increased expression and phosphorylation of tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis), as well as changes in several genes known to regulate dopamine activity in the ventral tegmental area. These findings demonstrate the involvement of a circadian-associated gene, Clock, in regulating dopamine function and cocaine reward.