Volkow Nora D, Wang Gene-Jack, Fowler Joanna S, Telang Frank
National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
Philos Trans R Soc Lond B Biol Sci. 2008 Oct 12;363(1507):3191-200. doi: 10.1098/rstb.2008.0107.
Drugs and food exert their reinforcing effects in part by increasing dopamine (DA) in limbic regions, which has generated interest in understanding how drug abuse/addiction relates to obesity. Here, we integrate findings from positron emission tomography imaging studies on DA's role in drug abuse/addiction and in obesity and propose a common model for these two conditions. Both in abuse/addiction and in obesity, there is an enhanced value of one type of reinforcer (drugs and food, respectively) at the expense of other reinforcers, which is a consequence of conditioned learning and resetting of reward thresholds secondary to repeated stimulation by drugs (abuse/addiction) and by large quantities of palatable food (obesity) in vulnerable individuals (i.e. genetic factors). In this model, during exposure to the reinforcer or to conditioned cues, the expected reward (processed by memory circuits) overactivates the reward and motivation circuits while inhibiting the cognitive control circuit, resulting in an inability to inhibit the drive to consume the drug or food despite attempts to do so. These neuronal circuits, which are modulated by DA, interact with one another so that disruption in one circuit can be buffered by another, which highlights the need of multiprong approaches in the treatment of addiction and obesity.
药物和食物部分通过增加边缘区域的多巴胺（DA）来发挥其强化作用，这引发了人们对于理解药物滥用/成瘾与肥胖之间关系的兴趣。在此，我们整合了正电子发射断层扫描成像研究中关于DA在药物滥用/成瘾以及肥胖中作用的研究结果，并提出了这两种情况的共同模型。在滥用/成瘾和肥胖中，一种强化物（分别为药物和食物）的价值增强，而以其他强化物为代价，这是条件性学习以及在易感性个体（即遗传因素）中由于药物（滥用/成瘾）和大量美味食物（肥胖）的反复刺激导致奖励阈值重置的结果。在这个模型中，在接触强化物或条件线索期间，预期奖励（由记忆回路处理）过度激活奖励和动机回路，同时抑制认知控制回路，导致尽管试图抑制，但仍无法抑制对药物或食物的消费冲动。这些受DA调节的神经回路相互作用，使得一个回路的破坏可以被另一个回路缓冲，这突出了在成瘾和肥胖治疗中采用多管齐下方法的必要性。
