Gatsby Computational Neuroscience Unit.
Institut des Maladies Neurodégénératives, Université de Bordeaux.
Psychol Rev. 2017 Mar;124(2):130-153. doi: 10.1037/rev0000046. Epub 2017 Jan 16.
Drug addiction implicates both reward learning and homeostatic regulation mechanisms of the brain. This has stimulated 2 partially successful theoretical perspectives on addiction. Many important aspects of addiction, however, remain to be explained within a single, unified framework that integrates the 2 mechanisms. Building upon a recently developed homeostatic reinforcement learning theory, the authors focus on a key transition stage of addiction that is well modeled in animals, escalation of drug use, and propose a computational theory of cocaine addiction where cocaine reinforces behavior due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint. Simulations show that our new theory accounts for key behavioral and neurobiological features of addiction, most notably, escalation of cocaine use, drug-primed craving and relapse, individual differences underlying dose-response curves, and dopamine D2-receptor downregulation in addicts. The theory also generates unique predictions about cocaine self-administration behavior in rats that are confirmed by new experimental results. Viewing addiction as a homeostatic reinforcement learning disorder coherently explains many behavioral and neurobiological aspects of the transition to cocaine addiction, and suggests a new perspective toward understanding addiction. (PsycINFO Database Record
药物成瘾涉及大脑的奖励学习和体内平衡调节机制。这激发了两种在成瘾问题上部分成功的理论观点。然而，许多成瘾的重要方面仍然需要在一个单一的、统一的框架内得到解释，该框架整合了这两种机制。基于最近提出的一种内稳态强化学习理论，作者关注成瘾的一个关键过渡阶段，该阶段在动物模型中得到了很好的模拟，即药物使用的升级，并提出了一种可卡因成瘾的计算理论，该理论认为可卡因由于其快速的体内平衡矫正作用而强化行为，而其慢性使用则导致体内平衡设定点缓慢而持久的变化。模拟结果表明，我们的新理论解释了成瘾的关键行为和神经生物学特征，尤其是可卡因使用的升级、药物引发的渴求以及复吸、剂量反应曲线背后的个体差异以及成瘾者中多巴胺 D2 受体的下调。该理论还对大鼠可卡因自我给药行为产生了独特的预测，这些预测得到了新的实验结果的证实。将成瘾视为一种内稳态强化学习障碍，可以一致地解释向可卡因成瘾过渡的许多行为和神经生物学方面，并为理解成瘾提供了一个新的视角。
