Volkow Nora D, Fowler Joanna S, Wang Gene-Jack
Office of the Director, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 5274, MSC 9581, Bethesda, MD 20892, USA.
Neuropharmacology. 2004;47 Suppl 1:3-13. doi: 10.1016/j.neuropharm.2004.07.019.
Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets.
影像学研究已经提供了证据，证明人类大脑在个体成瘾时是如何变化的。在此，我们整合影像学研究的结果，提出一个药物成瘾模型。成瘾过程部分是由滥用药物引起的多巴胺（DA）快速且大幅增加所启动的。我们假设，药物的这种超生理效应会触发参与显著性/奖赏、动机/驱力、记忆/条件作用以及控制/去抑制的神经回路的一系列适应性变化，从而导致药物及其相关线索的显著性价值增强（且持久），代价是对日常生活中的显著事件（包括自然强化物）的敏感性降低。虽然急性药物摄入会增加多巴胺神经传递，但长期药物消费会导致多巴胺活性显著下降，这与眶额皮质（参与显著性归因的区域）和扣带回（参与抑制控制的区域）的失调等有关。随后，对药物的动机驱力增加，通过条件反应得到强化，并且抑制控制的降低有利于强迫性药物使用的出现。这种关于滥用药物如何影响大脑的观点提示了干预策略，其中可能包括：（a）那些将降低首选药物奖赏价值的策略；（b）增加非药物强化物显著性价值的干预措施；（c）削弱条件性药物行为的方法；以及（d）加强额叶抑制和执行控制的方法。尽管这个模型主要关注大脑多巴胺系统的正电子发射断层扫描（PET）研究结果，但很明显其他神经递质也参与其中，并且更好地理解它们在成瘾中的作用将扩大治疗靶点的选择范围。
