Crews Fulton T, Vetreno Ryan P, Broadwater Margaret A, Robinson Donita L
Bowles Center for Alcohol Studies (F.T.C., R.P.V., M.A.B., D.L.R.), Department of Psychiatry (F.T.C., D.L.R.), and Department of Pharmacology (F.T.C.), School of Medicine, University of North Carolina, Chapel Hill, North Carolina
Bowles Center for Alcohol Studies (F.T.C., R.P.V., M.A.B., D.L.R.), Department of Psychiatry (F.T.C., D.L.R.), and Department of Pharmacology (F.T.C.), School of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Pharmacol Rev. 2016 Oct;68(4):1074-1109. doi: 10.1124/pr.115.012138.
Adolescence is a developmental period when physical and cognitive abilities are optimized, when social skills are consolidated, and when sexuality, adolescent behaviors, and frontal cortical functions mature to adult levels. Adolescents also have unique responses to alcohol compared with adults, being less sensitive to ethanol sedative-motor responses that most likely contribute to binge drinking and blackouts. Population studies find that an early age of drinking onset correlates with increased lifetime risks for the development of alcohol dependence, violence, and injuries. Brain synapses, myelination, and neural circuits mature in adolescence to adult levels in parallel with increased reflection on the consequence of actions and reduced impulsivity and thrill seeking. Alcohol binge drinking could alter human development, but variations in genetics, peer groups, family structure, early life experiences, and the emergence of psychopathology in humans confound studies. As adolescence is common to mammalian species, preclinical models of binge drinking provide insight into the direct impact of alcohol on adolescent development. This review relates human findings to basic science studies, particularly the preclinical studies of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium. These studies focus on persistent adult changes in neurobiology and behavior following adolescent intermittent ethanol (AIE), a model of underage drinking. NADIA studies and others find that AIE results in the following: increases in adult alcohol drinking, disinhibition, and social anxiety; altered adult synapses, cognition, and sleep; reduced adult neurogenesis, cholinergic, and serotonergic neurons; and increased neuroimmune gene expression and epigenetic modifiers of gene expression. Many of these effects are specific to adolescents and not found in parallel adult studies. AIE can cause a persistence of adolescent-like synaptic physiology, behavior, and sensitivity to alcohol into adulthood. Together, these findings support the hypothesis that adolescent binge drinking leads to long-lasting changes in the adult brain that increase risks of adult psychopathology, particularly for alcohol dependence.
青春期是一个发育阶段，在此期间身体和认知能力得到优化，社交技能得以巩固，性取向、青少年行为以及额叶皮质功能发育成熟至成人水平。与成年人相比，青少年对酒精也有独特的反应，对乙醇的镇静运动反应不太敏感，这很可能导致暴饮和昏厥。人群研究发现，饮酒起始年龄较早与酒精依赖、暴力和受伤风险增加相关。大脑突触、髓鞘形成和神经回路在青春期发育至成人水平，与此同时，对行为后果的反思增加，冲动性和冒险寻求行为减少。酒精暴饮可能会改变人类发育，但人类的基因、同龄人群体、家庭结构、早期生活经历以及精神病理学的出现等因素使得相关研究变得复杂。由于青春期在哺乳动物物种中很常见，暴饮的临床前模型有助于深入了解酒精对青少年发育的直接影响。本综述将人类研究结果与基础科学研究相关联，特别是成年期青少年饮酒神经生物学（NADIA）联盟的临床前研究。这些研究聚焦于青少年间歇性乙醇（AIE）（一种未成年饮酒模型）后成年期神经生物学和行为的持续变化。NADIA研究及其他研究发现，AIE会导致以下结果：成年后饮酒量增加、行为抑制解除和社交焦虑；成年后突触、认知和睡眠改变；成年后神经发生、胆碱能和5-羟色胺能神经元减少；神经免疫基因表达和基因表达的表观遗传修饰增加。其中许多影响是青少年特有的，在成年期的平行研究中未发现。AIE可导致青少年样突触生理学、行为以及对酒精的敏感性持续至成年期。总之，这些发现支持了以下假设：青少年暴饮会导致成年大脑产生持久变化，增加成年期精神病理学风险，尤其是酒精依赖风险。
