Clapp Peter, Bhave Sanjiv V, Hoffman Paula L
Alcohol Res Health. 2008;31(4):310-39.
The development of alcohol dependence is posited to involve numerous changes in brain chemistry (i.e., neurotransmission) that lead to physiological signs of withdrawal upon abstinence from alcohol as well as promote vulnerability to relapse in dependent people. These neuroadaptive changes often occur in those brain neurotransmission systems that are most sensitive to the acute, initial effects of alcohol and/or contribute to a person’s initial alcohol consumption. Studies of these neuroadaptive changes have been aided by the development of animal models of alcohol dependence, withdrawal, and relapse behavior. These animal models, as well as findings obtained in humans, have shed light on the effects that acute and chronic alcohol exposure have on signaling systems involving the neurotransmitters glutamate, γaminobutyric acid (GABA), dopamine, and serotonin, as well as on other signaling molecules, including endogenous opioids and corticotrophin-releasing factor (CRF). Adaptation to chronic alcohol exposure by these systems has been associated with behavioral effects, such as changes in reinforcement, enhanced anxiety, and increased sensitivity to stress, all of which may contribute to relapse to drinking in abstinent alcoholics. Moreover, some of these systems are targets of currently available therapeutic agents for alcohol dependence.
酒精依赖的发展被认为涉及大脑化学（即神经传递）的众多变化，这些变化会导致戒酒时出现生理戒断症状，并使依赖者更容易复发。这些神经适应性变化通常发生在那些对酒精的急性初始作用最敏感和/或促成一个人最初饮酒行为的大脑神经传递系统中。酒精依赖、戒断和复发行为动物模型的发展有助于对这些神经适应性变化进行研究。这些动物模型以及在人类身上获得的研究结果，揭示了急性和慢性酒精暴露对涉及神经递质谷氨酸、γ-氨基丁酸（GABA）、多巴胺和5-羟色胺的信号系统以及对包括内源性阿片类物质和促肾上腺皮质激素释放因子（CRF）在内的其他信号分子的影响。这些系统对慢性酒精暴露的适应与行为效应有关，如强化作用的改变、焦虑增强和对压力的敏感性增加，所有这些都可能促使戒酒的酗酒者重新饮酒。此外，这些系统中的一些是目前可用的酒精依赖治疗药物的靶点。
