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易患成瘾的多巴胺波动:一种神经发育模型。

Dopamine ups and downs in vulnerability to addictions: a neurodevelopmental model.

机构信息

Department of Psychiatry, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Psychology, McGill University, Montreal, Quebec, Canada; Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.

Department of Psychiatry and Behavioral Neuroscience, The University of Chicago, Chicago, IL, USA; Committee on Neurobiology, The University of Chicago, Chicago, IL, USA.

出版信息

Trends Pharmacol Sci. 2014 Jun;35(6):268-76. doi: 10.1016/j.tips.2014.04.002. Epub 2014 Apr 30.

Abstract

Addictions are commonly presaged by problems in childhood and adolescence. For many individuals this starts with the early expression of impulsive risk-taking, social gregariousness, and oppositional behaviors. Here we propose that these early diverse manifestations reflect a heightened ability of emotionally salient stimuli to activate dopamine pathways that foster behavioral approach. If substance use is initiated, these at-risk youth can also develop heightened responses to drug-paired cues. Through conditioning and drug-induced sensitization, these effects strengthen and accumulate, leading to responses that exceed those elicited by other rewards. At the same time, cues not paired with drug become associated with comparatively lower dopamine release, accentuating further the difference between drug and non-drug rewards. Together, these enhancing and inhibiting processes steer a pre-existing vulnerability toward a disproportionate concern for drugs and drug-related stimuli. Implications for prevention and treatment are discussed.

摘要

成瘾通常预示着儿童和青少年时期的问题。对许多人来说,这始于冲动冒险、社交能力和对立行为的早期表现。在这里,我们提出这些早期的不同表现反映了情感刺激更强烈地激活多巴胺途径,从而促进行为接近。如果开始使用物质,这些处于危险中的年轻人也会对与药物相关的线索产生更高的反应。通过条件作用和药物引起的敏感化,这些影响会加强和积累,导致反应超过其他奖励引起的反应。与此同时,与药物不相关的线索与相对较低的多巴胺释放相关联,进一步强调了药物和非药物奖励之间的差异。这些增强和抑制过程共同将先前存在的脆弱性引导到对药物和与药物相关的刺激的不成比例的关注。讨论了预防和治疗的意义。

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