咖啡因的觉醒效应取决于伏隔核壳部的腺苷 A2A 受体。
Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.
机构信息
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
出版信息
J Neurosci. 2011 Jul 6;31(27):10067-75. doi: 10.1523/JNEUROSCI.6730-10.2011.
Abstract
Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A(2A)Rs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.
摘要
咖啡因是最广泛使用的精神活性化合物，是一种腺苷受体拮抗剂。它通过阻断大脑中的腺苷 A（2A）受体（A（2A）R）来促进觉醒，但尚未确定咖啡因作用于产生觉醒的特定神经元。我们使用基于 Cre/loxP 技术的选择性基因缺失策略，以及通过携带短发夹 RNA 的腺相关病毒局部感染大鼠来沉默 A（2A）R 的表达，报告说，壳核（NAc）的 A（2A）R 负责咖啡因对觉醒的影响。当从 NAc 核心或基底神经节的其他 A（2A）R 阳性区域局部去除 A（2A）R 时，咖啡因引起的觉醒在大鼠中不受影响。我们的观察结果表明，咖啡因通过激活传统上与大脑中的动机和运动反应相关的途径来促进觉醒。
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