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Effects of Chronic ethanol exposure in male and female adolescents on behavior an

男性和女性青少年长期接触乙醇对行为和行为的影响

基本信息

批准号：
7809677
负责人：
CHERYL L KIRSTEIN
金额：
$ 17.7万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-01 至 2011-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Elucidating the impact of alcohol on the adolescent brain is of paramount importance not only to understand the nature of the addictive process but also to prevent the progression from casual alcohol use to dependency. The overall goal of this proposal is to test the hypothesis that the adolescent brain is uniquely susceptible to physiological changes induced by ethanol and that these ethanol-induced perturbations during adolescence persist into adulthood rendering the animals more vulnerable to its addicting effects. Specifically, we propose that ethanol exposure during adolescence alters key neuronal circuitry and that these changes persist into adulthood with consequent changes in the normal functions of this pathway that may be responsible for the predisposition of the "ethanol-exposed" brain to ethanol use as compared to the "ethanol-naive" brain. The proposed experiments are designed to determine sex differences in the long-term effects of chronic exposure to experimenter administered ethanol (or saline) during adolescence [postnatal day (PND) 30-50] or adulthood (PND 60-80) in male and female rats. Following ethanol (or saline) exposure, adolescent-exposed and adult- exposed rats will be tested as adults (PND 74 or PND 104, respectively) for the effects of ethanol preexposure on ethanol consumption via voluntary sweetened ethanol intake (Specific Aim 1). For a neurochemical measure, ethanol-induced dopaminergic responses of the nucleus accumbens septi, likely to be affected and involved sequentially in the progression from alcohol use to alcohol dependency, will be measured in response to experimenter-administered ethanol (0.75, 1.75 g/kg/ip ethanol) or saline using in vivo microdialysis (Specific Aim 2). Blood and brain ethanol concentrations will be examined in all proposed experiments to determine possible sex and pretreatment differences in the metabolism of ethanol. Additionally, estrous cycling will be evaluated in all females during adulthood to investigate the effects of changes in the estrous cycle on long term behavioral and neurochemical consequences of chronic ethanol exposure during adolescence or adulthood. Results from these studies will clearly delineate the lasting impact of chronic exposure to ethanol during adolescence as compared to adulthood on the subsequent adult brain and behavior. Information on the alteration of ethanol consumption patterns and neurochemical processes of the brain that render animals susceptible to ethanol addiction is critically important for understanding the addictive process and how it may be prevented or treated. PUBLIC HEALTH RELEVANCE: These studies will examine the long term effects of ethanol on the adult male and female brain and behavior following ethanol exposure during adolescence or adulthood.

描述（由申请人提供）：阐明酒精对青少年大脑的影响至关重要，不仅对于理解成瘾过程的本质，而且对于防止从随意饮酒发展为依赖。该提案的总体目标是检验以下假设：青少年大脑特别容易受到乙醇引起的生理变化的影响，并且这些乙醇在青春期引起的扰动持续到成年期，使动物更容易受到其成瘾作用的影响。具体来说，我们提出，青春期期间的乙醇暴露会改变关键的神经元回路，并且这些变化持续到成年期，从而导致该通路的正常功能发生变化，这可能是与“未接触过乙醇”的大脑相比，“暴露于乙醇”的大脑更容易使用乙醇的原因。拟议的实验旨在确定雄性和雌性大鼠在青春期 [出生后 (PND) 30-50] 或成年期 (PND 60-80) 期间长期暴露于实验者施用的乙醇（或盐水）的长期影响的性别差异。暴露于乙醇（或盐水）后，青少年暴露和成年暴露的大鼠将作为成年大鼠（分别为 PND 74 或 PND 104）进行测试，以了解乙醇预暴露对自愿摄入加糖乙醇的乙醇消耗的影响（具体目标 1）。对于神经化学测量，乙醇诱导的伏隔核多巴胺能反应可能会受到影响，并依次参与从饮酒到酒精依赖的进展，将使用体内微透析（具体目标 2）对实验者施用的乙醇（0.75、1.75 g/kg/ip 乙醇）或盐水进行测量。在所有拟议的实验中都将检查血液和脑中的乙醇浓度，以确定乙醇代谢中可能存在的性别和治疗前差异。此外，将对所有女性成年期间的发情周期进行评估，以研究发情周期的变化对青春期或成年期间慢性乙醇暴露的长期行为和神经化学后果的影响。这些研究的结果将清楚地描绘出与成年期相比，青春期长期接触乙醇对随后成年大脑和行为的持久影响。关于乙醇消耗模式和大脑神经化学过程的改变（使动物容易对乙醇成瘾）的信息对于理解成瘾过程以及如何预防或治疗它至关重要。公共卫生相关性：这些研究将研究乙醇对成年男性和女性大脑以及青春期或成年期间接触乙醇后行为的长期影响。