Rearing-induced Plasticity and Incentive Motivation for Ethanol

项目总结 酒精中毒的一个特征是对乙醇的激励动机增加。激励动机是 包括对乙醇做出反应的动机和乙醇的享乐价值。早早饮酒 发病与较早发病的酒精中毒、较严重的酒精依赖有关，以及 神经元微结构缺陷增加。而男性和女性的饮酒率相对较低 与青春期类似，青春期接触乙醇会对大脑造成更大的损害 女性的神经元微结构，而更多的男性在成年后出现酒精使用障碍。在……里面 啮齿动物，童年和青春期不同的养育环境导致了可塑性- 依赖性神经元改变。这些神经元的变化影响了各种行为，包括 对乙醇的反应。在丰富的条件下饲养大鼠可以减少对操作液中乙醇的反应 与在隔离或标准条件下饲养的大鼠相比，乙醇自我给药。这个 所提出的实验的首要目标是确定差异养育是否诱导了可塑性 改变神经元微结构的完整性，以影响享乐性价值和激励。 成年期对酒精的显著需求。据推测，饲养雄性和雌性大鼠在一个 与饲养雄性和雌性相比，环境会降低对酒精的享乐反应 隔离或标准环境中的老鼠。拟议中的实验还将确定差异是否 青少年间歇性酒精暴露期间的教养可以改变享乐主义的价值和激励 成年期对酒精的显著需求。据预测，青少年酒精暴露期间的浓缩物 无论是雄性还是雌性大鼠，都能预防成年后酒精中毒风险的增加。这个 拟议的实验将检验在青少年酒精暴露期间不同的养育方式 利用扩散张力成像改变神经元的微观结构。据预测，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 与在与世隔绝或社会条件下饲养的老鼠相比。我们进一步预测，性行为将改变 青少年酒精暴露对神经元微结构完整性及女性的影响 由于青春期的酒精，隔离的大鼠对神经元微结构的损害最大 曝光。该项目的完成将决定不同的养育方式改变对 乙醇引起的神经元微结构完整性的改变。这一模式的开发将提供 美国测试青少年酒精引起的行为和神经生物学变化的能力 暴露在临床前模型系统中，导致可塑性和乙醇的不同结果 敏感度。

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.