Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.)
Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
Pharmacol Rev. 2015 Oct;67(4):872-1004. doi: 10.1124/pr.115.010967.
Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses.
神经系统对不同化学和生理条件的适应对于大脑过程的内稳态以及学习和记忆对挑战的适当反应非常重要。尽管人们早就知道各种滥用药物的耐受和依赖等过程，但最近发现，即使是各种滥用药物的单次药理相关剂量也会在选定的神经元群体中诱导神经可塑性，例如腹侧被盖区的多巴胺神经元，这些变化在药物排出后很长时间内仍然存在。长期（自我）给药会导致许多脑细胞群体的基因表达、神经化学、神经生理学和结构发生变化。这些特定于区域的变化与成瘾、药物摄入以及条件性药物效应相关，例如线索或应激引发的药物寻求复燃。在啮齿动物中，青春期暴露于药物通常会导致成年后出现更明显的行为变化，比相应的成年暴露更为显著。在临床上，胎儿发育过程中酒精对大脑造成的损伤最为严重和破坏性。在成年娱乐性药物使用者或接受药物治疗的患者中，很难发现持续的功能或行为变化，这表明需要大量接触滥用药物才会导致神经毒性和持续的情绪和认知改变。这篇综述描述了该重要研究领域的最新进展，其目标是将这些知识转化为更好的成瘾和相关神经精神疾病的治疗方法。
