Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Neurobiol Learn Mem. 2011 Nov;96(4):609-23. doi: 10.1016/j.nlm.2011.02.014. Epub 2011 Mar 3.
Over the past several years, drug addiction has increasingly been accepted to be a disease of the brain as opposed to simply being due to a lack of willpower or personality flaw. Exposure to addictive substances has been shown to create enduring changes in brain structure and function that are thought to underlie the transition to addiction. Specific genetic and environmental vulnerability factors also influence the impact of drugs of abuse on the brain and can enhance the likelihood of becoming an addict. Long-lasting alterations in brain function have been found in neural circuits that are known to be responsible for normal appetitive learning and memory processes and it has been hypothesized that drugs of abuse enhance positive learning and memory about the drug while inhibiting learning about the negative consequences of drug use. Therefore, the addict's behavior becomes increasingly directed towards obtaining and using drugs of abuse, while at the same time developing a poorer ability to stop using, even when the drug is less rewarding or interferes with functioning in other facets of life. In this review we will discuss the clinical evidence that addicted individuals have altered learning and memory and describe the possible neural substrates of this dysfunction. In addition, we will explore the pre-clinical evidence that drugs of abuse cause a progressive disorder of learning and memory, review the molecular and neurobiological changes that may underlie this disorder, determine the genetic and environmental factors that may increase vulnerability to addiction, and suggest potential strategies for treating addiction through manipulations of learning and memory.
在过去的几年中，人们越来越接受这样一种观点，即药物成瘾是一种大脑疾病，而不仅仅是由于缺乏意志力或个性缺陷。研究表明，接触成瘾物质会导致大脑结构和功能的持久变化，这些变化被认为是成瘾转变的基础。特定的遗传和环境易感性因素也会影响滥用药物对大脑的影响，并增加成为瘾君子的可能性。在已知负责正常食欲学习和记忆过程的神经回路中，已经发现了大脑功能的持久改变，并且有人假设滥用药物会增强对药物的积极学习和记忆，同时抑制对药物使用的负面后果的学习。因此，瘾君子的行为越来越倾向于获取和使用滥用药物，同时发展出较差的停止使用能力，即使药物的奖励减少或干扰生活其他方面的功能。在这篇综述中，我们将讨论成瘾者学习和记忆改变的临床证据，并描述这种功能障碍的可能神经基础。此外，我们将探讨滥用药物导致学习和记忆进行性障碍的临床前证据，回顾可能导致这种障碍的分子和神经生物学变化，确定可能增加成瘾易感性的遗传和环境因素，并通过学习和记忆的操纵提出治疗成瘾的潜在策略。
