Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome
Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome
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DOI：
10.1002/ajmg.b.30080
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发表时间：
2005-01-05
影响因子：
2.8
通讯作者：
Oscar-Berman, M
中科院分区：
文献类型：
--
作者：
Bowirrat, A;Oscar-Berman, M
在这篇综述中，我们描述了奖励缺乏综合征的神经基质，反过来，它被认为是酒精依赖的基础。酒精中毒是一种复杂的多因素疾病，是遗传和环境因素相互作用的结果。D-2多巴胺受体（DRD 2）与快乐有关，DRD 2 A1等位基因被称为奖励基因。有证据表明，多巴胺受体缺乏、酗酒倾向和对奖励的敏感性降低三者之间存在相互作用。这种相互作用在很大程度上依赖于个人的遗传特征，某些种族群体比其他人更倾向于酗酒。DRD 2是神经精神疾病中最广泛研究的基因之一，特别是在酒精中毒和其他成瘾中。多巴胺D-2（DRD 2）基因，特别是其等位基因TaqI A1等位基因及其受体，也可能参与共病的反社会人格障碍症状，高新奇寻求和相关特征。中皮质边缘多巴胺能通路系统在介导滥用药物的强化中起着特别重要的作用，并且它可能是成瘾如酒精中毒的共同特征。当中脑皮质边缘多巴胺奖赏系统功能障碍时（可能是由某些遗传变异引起的），最终的结果是奖赏缺乏综合征和随后的药物寻求行为。奖赏缺乏综合征是指由于遗传和环境的影响，奖赏级联的崩溃，以及由此产生的异常行为。酒精和其他滥用药物以及大多数正强化剂会导致大脑多巴胺的激活和神经元释放，从而减少负面情绪并满足异常的渴望。DRD 2受体的缺乏或缺失则使个体易于发生多种成瘾，冲动和强迫行为的高风险。虽然其他神经递质（例如，谷氨酸、γ-氨基丁酸（GABA）和5-羟色胺）在决定乙醇的奖励和刺激作用方面可能是重要的，多巴胺可能是开始使用药物和在长期禁欲期间恢复使用药物的关键。这篇文章包含补充材料，可以在美国医学遗传学杂志网站http：//www.example.com上查看。www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html (C)2004 Wiley-Liss，Inc.
In this review, we described the neural substrates underlying Reward Deficiency syndrome which, in turn, is posited to underlie alcohol dependency. Alcoholism is a complex, multifactorial disorder that results from the interplay between genetic and environmental factors. The D-2 dopamine receptor (DRD2) has been associated with pleasure, and the DRD2 A1 allele has been referred to as a reward gene. Evidence suggests that there is a tripartite interaction involving dopamine receptor deficiency, a propensity to abuse alcohol, and reduced sensitivity to rewards. This interaction relies heavily on genetic characteristics of the individual, with certain ethnic groups having a greater tendency toward alcoholism than others. The DRD2 has been one of the most widely studied in neuropsychiatric disorders in general, and in alcoholism and other addictions in particular. The dopamine D-2 (DRD2) gene, and especially its allele TaqI A1 allele and its receptor, also may be involved in comorbid antisocial personality disorder symptoms, high novelty seeking, and related traits. The mesocorticolimbic dopaminergic pathway system plays an especially important role in mediating reinforcement by abused drugs, and it may be a common denominator for addictions such as alcoholism. When the mesocorticolimbic dopamine reward system dysfunctions (perhaps caused by certain genetic variants), the end result is Reward Deficiency syndrome and subsequent drug-seeking behaviors. Reward Deficiency syndrome refers to the breakdown of the reward cascade, and resultant aberrant conduct, due to genetic and environmental influences. Alcohol and other drugs of abuse, as well as most positive reinforcers, cause activation and neuronal release of brain dopamine, which can decrease negative feelings and satisfy abnormal cravings. A deficiency or absence of DRD2 receptors then predisposes individuals to a high risk for multiple addictive, impulsive, and compulsive behaviors. Although other neurotransmitters (e.g., glutamate, gamma-aminobutyric acid (GABA), and serotonin) may be important in determining the rewarding and stimulating effects of ethanol, dopamine may be critical for initiating drug use and for reinstating drug use during protracted abstinence. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http:// www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html. (C) 2004 Wiley-Liss, Inc.