Zack Martin, Poulos Constantine X
Clinical Neuroscience Section, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.
Curr Drug Abuse Rev. 2009 Jan;2(1):11-25. doi: 10.2174/1874473710902010011.
A variety of evidence suggests important commonalities in the neurochemical basis of reinforcement in pathological gambling (PG) and psychostimulant addiction. This article focuses on the parallel and specific roles that dopamine (DA) activation plays in these two disorders, beyond its generic role in reinforcement. A psychostimulant-mimetic model for PG is proposed based on evidence from the following domains: Acute subjective-behavioral effects of gambling and psychostimulants; Effects of anticipated rewards and uncertainty of reward delivery (key elements of gambling) on DA release; Relationship between DA release and positive arousal; Cross-priming of motivation for gambling by amphetamine; Effects of DA D2 antagonists on gambling and amphetamine reward; Effects of mixed D1-D2 antagonists on clinical symptoms of PG; Effects of DA D2 agonists on experimental measures of risk-taking, gambling, and induction of PG in patients with Parkinson's disease; Electrophysiological and cognitive disturbances associated with chronic exposure to gambling and psychostimulants, and the possible role of sensitization in these effects. Limitations of the model regarding the exclusive role of DA are discussed with particular reference to genetic risk, co-morbidity, and sub-types of PG. Suggestions for future research include isolating the roles of DA receptor subtypes in PG, and parallel within-subject assessment of DA manipulations on gambling and psychostimulant reinforcement in PG subjects and controls.
多种证据表明,病理性赌博(PG)和精神兴奋剂成瘾在强化作用的神经化学基础方面存在重要的共性。本文重点探讨多巴胺(DA)激活在这两种疾病中所起的平行且特定的作用,而非其在强化作用中的一般作用。基于以下领域的证据,提出了一种PG的精神兴奋剂模拟模型:赌博和精神兴奋剂的急性主观行为效应;预期奖励和奖励发放的不确定性(赌博的关键要素)对DA释放的影响;DA释放与积极唤醒之间的关系;苯丙胺对赌博动机的交叉启动作用;DA D2拮抗剂对赌博和苯丙胺奖励的影响;D1-D2混合拮抗剂对PG临床症状的影响;DA D2激动剂对帕金森病患者冒险行为、赌博及PG诱导实验指标的影响;与长期接触赌博和精神兴奋剂相关的电生理和认知障碍,以及敏化作用在这些影响中可能发挥的作用。文中讨论了该模型在DA的唯一作用方面的局限性,特别提及了遗传风险、共病情况以及PG的亚型。对未来研究的建议包括明确DA受体亚型在PG中的作用,以及在PG患者和对照组中对DA操纵对赌博和精神兴奋剂强化作用进行平行的个体内评估。