Addiction is a disease characterized by compulsive drug seeking and consumption observed in 20-30% of users. An addicted individual will favor drug reward over natural rewards, despite major negative consequences. Mechanistic research on rodents modeling core components of the disease has identified altered synaptic transmission as the functional substrate of pathological behavior. While the initial version of a circuit model for addiction focused on early drug adaptive behaviors observed in all individuals, it fell short of accounting for the stochastic nature of the transition to compulsion. The model builds on the initial pharmacological effect common to all addictive drugs-an increase in dopamine levels in the mesolimbic system. Here, we consolidate this early model by integrating circuits underlying compulsion and negative reinforcement. We discuss the genetic and epigenetic correlates of individual vulnerability. Many recent data converge on a gain-of-function explanation for circuit remodeling, revealing blueprints for novel addiction therapies. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

中文翻译：

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合并成瘾电路模型。

成瘾是一种以强迫性药物寻找和消费为特征的疾病，在20-30％的使用者中观察到。上瘾的个人尽管有重大负面后果，但还是会偏爱药物奖励而不是自然奖励。对啮齿类动物疾病的核心成分进行建模的机械研究已经确定，突触传递的改变是病理行为的功能基础。虽然成瘾回路模型的最初版本侧重于在所有个体中观察到的早期药物适应性行为，但并没有考虑到强迫症过渡的随机性。该模型建立在所有成瘾药物普遍具有的初始药理作用基础上-中脑边缘系统中多巴胺水平的增加。在这里，我们通过集成强迫和负强化下面的电路来巩固这个早期模型。我们讨论了个体脆弱性的遗传和表观遗传相关性。最近的许多数据集中在功能获得的电路重塑说明上，揭示了新的成瘾疗法的蓝图。《神经科学年度评论》（第44卷）的最终最终在线发布日期为2021年7月。有关修订的估算，请参见http://www.annualreviews.org/page/journal/pubdates。