Volkow Nora D, Fowler Joanna S, Wang Gene-Jack, Swanson James M, Telang Frank
National Institute on Drug Abuse, 6001 Executive Blvd, Room 5274-MSC 9581, Bethesda, MD 20892, USA.
Arch Neurol. 2007 Nov;64(11):1575-9. doi: 10.1001/archneur.64.11.1575.
Imaging studies have provided new insights on the role of dopamine (DA) in drug abuse and addiction in the human brain. These studies have shown that the reinforcing effects of drugs of abuse in human beings are contingent not just on DA increases per se in the striatum (including the nucleus accumbens) but on the rate of DA increases. The faster the increases, the more intense the reinforcing effects. They have also shown that elevated levels of DA in the dorsal striatum are involved in the motivation to procure the drug when the addicted subject is exposed to stimuli associated with the drug (conditioned stimuli). In contrast, long-term drug use seems to be associated with decreased DA function, as evidenced by reductions in D2 DA receptors and DA release in the striatum in addicted subjects. Moreover, the reductions in D2 DA receptors in the striatum are associated with reduced activity of the orbitofrontal cortex (region involved with salience attribution and motivation and with compulsive behaviors) and of the cingulate gyrus (region involved with inhibitory control and impulsivity), which implicates deregulation of frontal regions by DA in the loss of control and compulsive drug intake that characterizes addiction. Because DA cells fire in response to salient stimuli and facilitate conditioned learning, their activation by drugs will be experienced as highly salient, driving the motivation to take the drug and further strengthening conditioned learning and producing automatic behaviors (compulsions and habits).
影像学研究为多巴胺（DA）在人类大脑药物滥用和成瘾中的作用提供了新的见解。这些研究表明，滥用药物对人类的强化作用不仅取决于纹状体（包括伏隔核）中DA本身的增加，还取决于DA增加的速率。增加得越快，强化作用就越强烈。研究还表明，当成瘾者接触与药物相关的刺激（条件刺激）时，背侧纹状体中升高的DA水平与获取药物的动机有关。相反，长期药物使用似乎与DA功能下降有关，成瘾者纹状体中D2 DA受体减少和DA释放减少就证明了这一点。此外，纹状体中D2 DA受体的减少与眶额皮质（参与显著性归因、动机和强迫行为的区域）和扣带回（参与抑制控制和冲动性的区域）的活动减少有关，这意味着DA对额叶区域的调节失控，导致成瘾所特有的失控和强迫性药物摄入。由于DA细胞对显著刺激产生反应并促进条件学习，药物对它们的激活会被体验为高度显著，从而驱动服药动机，并进一步加强条件学习，产生自动行为（强迫行为和习惯）。
