Subsecond dopamine release promotes cocaine seeking
Subsecond dopamine release promotes cocaine seeking
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DOI：
10.1038/nature01566
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发表时间：
2003-04-10
期刊：
影响因子：
64.8
通讯作者：
Carelli, RM
中科院分区：
文献类型：
--
作者：
Phillips, PEM;Stuber, GD;Carelli, RM
从中脑腹侧被盖区到脑桥核的含多巴胺投射在介导可卡因的强化特性中起着关键作用（1，2）。虽然这一区域的神经元在亚秒的时间尺度上对奖励做出反应（3，4），但神经化学研究仅通过检查细胞外多巴胺的紧张（分钟到分钟）水平的变化来解决多巴胺在药物成瘾中的作用（5-9）。为了研究阶段性（亚秒）多巴胺信号传导的作用（10），我们使用电化学技术（11）每100 ms测量一次丘脑核中的多巴胺。在大鼠服药行为的关键方面观察到细胞外多巴胺浓度的快速变化。在杠杆按压可卡因之前，多巴胺的增加与寻求药物行为的开始相一致。值得注意的是，这些行为可以通过在这个时间尺度上电诱发多巴胺释放来再现。杠杆按压后，在可卡因相关线索的同时呈现时多巴胺浓度进一步增加。这些线索本身也引发了类似的，快速的多巴胺信号，但只有在动物中，他们以前配对可卡因交付。这些发现揭示了多巴胺在真实的时间内对药物服用的调节中所起的前所未有的作用。
The dopamine-containing projection from the ventral tegmental area of the midbrain to the nucleus accumbens is critically involved in mediating the reinforcing properties of cocaine(1,2). Although neurons in this area respond to rewards on a subsecond timescale(3,4), neurochemical studies have only addressed the role of dopamine in drug addiction by examining changes in the tonic (minute-to-minute) levels of extracellular dopamine(5-9). To investigate the role of phasic (subsecond) dopamine signalling(10), we measured dopamine every 100 ms in the nucleus accumbens using electrochemical technology(11). Rapid changes in extracellular dopamine concentration were observed at key aspects of drug-taking behaviour in rats. Before lever presses for cocaine, there was an increase in dopamine that coincided with the initiation of drug-seeking behaviours. Notably, these behaviours could be reproduced by electrically evoking dopamine release on this timescale. After lever presses, there were further increases in dopamine concentration at the concurrent presentation of cocaine-related cues. These cues alone also elicited similar, rapid dopamine signalling, but only in animals where they had previously been paired to cocaine delivery. These findings reveal an unprecedented role for dopamine in the regulation of drug taking in real time.