Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.
Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.
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DOI：
10.1523/jneurosci.6730-10.2011
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发表时间：
2011-07-06
期刊：
影响因子：
--
通讯作者：
Chen JF
中科院分区：
文献类型：
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作者：
Lazarus M;Shen HY;Cherasse Y;Qu WM;Huang ZL;Bass CE;Winsky-Sommerer R;Semba K;Fredholm BB;Boison D;Hayaishi O;Urade Y;Chen JF
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 A2A 受体 (A2AR) 来促进觉醒，但咖啡因产生唤醒作用的特定神经元尚未确定。我们利用基于小鼠 Cre/loxP 技术的选择性基因删除策略，以及局灶性 RNA 干扰，通过携带短发夹 RNA 的腺相关病毒局部感染来沉默大鼠中 A2AR 的表达，我们发现伏隔核 (NAc) 外壳区域的 A2AR 是咖啡因对觉醒的影响的原因。当 A2AR 从 NAc 核心或基底神经节的其他 A2AR 阳性区域局部去除时，咖啡因诱导的唤醒不会受到影响。我们的观察表明，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。
Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A2A receptors (A2ARs) 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 A2ARs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A2ARs 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 A2ARs were focally removed from the NAc core or other A2AR-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.