Rearing-induced Plasticity and Incentive Motivation for Ethanol

项目摘要 酒精中毒的一个特点是对乙醇的刺激动机增加。激励动机是 包括对乙醇的反应动机和乙醇的享乐价值。早期饮酒 发病与酒精中毒的早期发病、酒精依赖的严重程度更高有关， 神经元微结构缺陷增加。虽然男性和女性的饮酒率相对较低， 与青春期相似，青春期接触乙醇会导致更多的损害， 在成年期，女性的神经元微结构发生变化，而更多的男性出现酒精使用障碍。在 啮齿类动物，儿童期和青少年期的不同养育环境导致可塑性- 依赖性神经元变化。这些神经元的变化会影响各种行为，包括 乙醇的反应。在丰富的条件下饲养大鼠降低了对乙醇的反应， 与在隔离或标准条件下饲养的大鼠相比，乙醇自我给药。的 提出的实验的首要目标是确定是否差异饲养诱导的可塑性 改变神经元微结构的完整性，从而影响享乐价值和激励 酒精在成年期的重要性据推测，饲养雄性和雌性大鼠在丰富的 环境将降低享乐反应乙醇相比，饲养男性和女性 大鼠在隔离或标准环境中。拟议的实验还将确定是否存在差异 间歇性青少年乙醇暴露期间的养育可以改变享乐价值和激励 酒精在成年期的重要性据预测，在青少年接触乙醇期间， 将防止雄性和雌性大鼠成年后酗酒的风险增加。的 拟议的实验，然后将研究如何差异饲养在青少年乙醇暴露 使用扩散张力成像改变神经元微结构。据预测，饲养在一个 丰富的环境将保护青少年免受酒精暴露的有害影响 与在隔离或社会条件下饲养的大鼠相比。我们进一步预测，性将改变 青少年乙醇暴露对神经元微结构完整性的影响 由于青春期的乙醇，隔离的大鼠将对神经元微结构造成最大的损害 exposure.该项目的完成将确定差异饲养改变激励动机， 乙醇由于神经元微结构完整性的改变。该模型的开发将提供 我们有能力测试青少年酒精导致的行为和神经生物学变化 在临床前模型系统中暴露，导致可塑性和乙醇的不同结果 灵敏度

PROJECT SUMMARY A characteristic of alcoholism is an increased incentive motivation for ethanol. Incentive motivation is comprised of the motivation to respond for ethanol and the hedonic value of ethanol. Early drinking onset is correlated with an earlier onset of alcoholism, a stronger severity of alcohol dependence, and increased deficits in neuronal microstructure. While drinking rates in males and females are relatively similar during adolescence, exposure to ethanol during adolescence results in more damage to the neuronal microstructure in females while more males develop alcohol-use disorders in adulthood. In rodents, differential rearing environments during childhood and adolescence result in plasticity- dependent neuronal changes. These neuronal changes impact a variety of behaviors, including the response to ethanol. Rearing rats in an enriched condition decreases responding for ethanol in operant ethanol self-administration when compared to rats raised in an isolated or standard condition. The overarching goal of the proposed experiments is to determine if differential rearing-induced plasticity alters the integrity of the neuronal microstructure to affect both the hedonic value and the incentive salience for ethanol in adulthood. It is hypothesized that rearing male and female rats in an enriched environment will decrease hedonic responses to ethanol when compared to rearing male and female rats in an isolated or standard environment. The proposed experiments will also determine if differential rearing during intermittent adolescent ethanol exposure can alter the hedonic value and incentive salience for ethanol in adulthood. It is predicted that enrichment during adolescent ethanol exposure will protect against the increased risk for alcoholism in adulthood in both male and female rats. The proposed experiments will then examine how differential rearing during adolescent ethanol exposure alters the neuronal microstructure using diffusion tension imaging. It is predicted that rearing in an enriched environment will protect against the deleterious effects of ethanol exposure in adolescence when compared to rats reared in an isolated or social condition. We further predict that sex will alter the effects of adolescent ethanol exposure on neuronal microstructure integrity and therefore female isolated rats will have the most damage to the neuronal microstructure as a result of adolescent ethanol exposure. Completion of the project will determine that differential rearing alters incentive motivation for ethanol due to alterations of neuronal microstructure integrity. Development of this model will provide us the ability to test behavioral and neurobiological changes that result from adolescent ethanol exposure in a preclinical model system that results in divergent outcomes for both plasticity and ethanol sensitivity.