Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA.
Alcohol. 2010 Feb;44(1):67-80. doi: 10.1016/j.alcohol.2009.09.034.
The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Because of their extended period of adolescence, rhesus macaques are especially well suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables, such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin-releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence.
青少年饮酒是一个日益严重的问题,已成为酒精使用障碍病因学的重要研究课题。该研究的一个关键组成部分是开发青少年饮酒和酒精反应的动物模型。由于其青春期延长,恒河猴特别适合模拟与酒精相关的表型,这些表型有助于青少年对酒精的消费倾向。在这篇综述中,我们讨论了来自我们实验室的研究,这些研究调查了恒河猴青少年对急性酒精给药的初始反应和自愿自我给药范式中酒精的消耗。这些研究证实,青春期在行为和生理上都是一个动态变化的时期,酒精反应和酒精消耗受生命史变量的影响,如年龄、性别和同伴养育形式的不良早期经历。此外,改变 5-羟色胺、内源性阿片和促肾上腺皮质激素释放激素系统功能的遗传变异也被证明会影响生理和行为结果,在某些情况下,与早期经历相互作用表明基因与环境的相互作用。这些发现突出了与酒精反应和消耗有关的几个途径,即奖励、行为失控和对压力的易感性,并表明这些途径在青少年早期酒精暴露的早期阶段发挥作用。