Ross Stephen, Peselow Eric
Division of Alcoholism and Drug Abuse, Bellevue Hospital, NYU Langone Center of Excellence on Addiction, New York University School of Medicine, New York, NY 10016, USA.
Clin Neuropharmacol. 2009 Sep-Oct;32(5):269-76. doi: 10.1097/wnf.0b013e3181a9163c.
Addiction is increasingly understood as a neurobiological illness where repetitive substance abuse corrupts the normal circuitry of rewarding and adaptive behaviors causing drug-induced neuroplastic changes. The addictive process can be examined by looking at the biological basis of substance initiation to the progression of substance abuse to dependence to the enduring risk of relapse. Critical neurotransmitters and neurocircuits underlie the pathological changes at each of these stages. Enhanced dopamine transmission in the nucleus accumbens is part of the common pathway for the positively rewarding aspects of drugs of abuse and for initiation of the addictive process. F-Aminobutyric acid,opioid peptides, serotonin, acetylcholine, the endocannabinoids, and glutamate systems also play a role in the initial addictive process. Dopamine also plays a key role in conditioned responses to drugs of abuse, and addiction is now recognized as a disease of pathological learning and memory. In the path from substance abuse to addiction, the neurochemistry shifts from a dopamine-based behavioral system to a predominantly glutamate-based one marked by dysregulated glutamate transmission from the prefrontal cortex to the nucleus accumbens in relation to drug versus biologically oriented stimuli. This is a core part of the executive dysfunction now understood as one of the hallmark features of addiction that also includes impaired decision making and impulse dysregulation.Understanding the neurobiology of the addictive process allows for a theoretical psychopharmacological approach to treating addictive disorders,one that takes into account biological interventions aimed at particular stages of the illness.
成瘾越来越被理解为一种神经生物学疾病，其中反复滥用药物会破坏奖励和适应性行为的正常神经回路，导致药物引起的神经可塑性变化。成瘾过程可以通过研究从药物使用起始的生物学基础到药物滥用发展为依赖再到复发的持久风险来进行考察。关键的神经递质和神经回路是这些阶段中每个阶段病理变化的基础。伏隔核中多巴胺传递增强是滥用药物积极奖励方面以及成瘾过程起始的共同途径的一部分。γ-氨基丁酸、阿片肽、血清素、乙酰胆碱、内源性大麻素和谷氨酸系统在最初的成瘾过程中也发挥作用。多巴胺在对滥用药物的条件反应中也起关键作用，现在成瘾被认为是一种病理性学习和记忆疾病。在从药物滥用到成瘾的过程中，神经化学从基于多巴胺的行为系统转变为主要基于谷氨酸的系统，其特征是与药物刺激和生物导向刺激相关的从额叶前皮质到伏隔核的谷氨酸传递失调。这是执行功能障碍的核心部分，现在被理解为成瘾的标志性特征之一，还包括决策受损和冲动调节障碍。了解成瘾过程的神经生物学为治疗成瘾性疾病提供了一种理论性的心理药理学方法，这种方法考虑到针对疾病特定阶段的生物干预措施。
