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Rearing-induced Plasticity and Incentive Motivation for Ethanol

饲养诱导的可塑性和乙醇的激励动机

基本信息

批准号：
10197945
负责人：
Mary Eileen Cain
金额：
$ 25.42万
依托单位：
KANSAS STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10197945
关键词：
21 year old Adolescence Adolescent Adult Adverse effects Affect Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Animal Model Animals Appetitive Behavior Behavior Behavioral Biological Models Brain Brain region Characteristics Childhood Cognitive Consummatory Behavior Cues Dependence Development Diffusion Diffusion Magnetic Resonance Imaging Environment Ethanol Faculty Female Female Adolescents Goals Human Image Incentives Individual Intravenous Literature Measures Mediating Motivation Neurobiology Neuronal Plasticity Neurons Oral Outcome Pre-Clinical Model Predisposition Rattus Research Rewards Risk Rodent Role Self Administration Severities Social Conditions Structure Synapses Synaptic plasticity Taste Perception Testing United States adolescent alcohol effect adolescent alcohol exposure adolescent binge drinking alcohol effect alcohol exposure alcohol response alcohol sensitivity alcohol use disorder behavior test binge drinking critical period drinking drinking onset early drinking early-onset alcoholism effective intervention environmental enrichment for laboratory animals experimental study gray matter hedonic incentive salience male model development neuromechanism reinforcer response sex sweet taste perception synaptic pruning underage drinking white matter

项目摘要

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.

项目概要酗酒的一个特征是对乙醇的激励动机增强。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。早期饮酒发病与酒精中毒较早发作、酒精依赖程度较严重相关，并且神经元微观结构的缺陷增加。虽然男性和女性的饮酒率相对较高与青春期相似，青春期接触乙醇会导致更大的损伤女性的神经元微观结构，而更多的男性在成年后出现酒精使用障碍。在啮齿动物，童年和青春期的不同饲养环境导致可塑性- 依赖性神经元变化。这些神经元变化影响多种行为，包括对乙醇的反应。在丰富的条件下饲养大鼠会降低操作者对乙醇的反应与在隔离或标准条件下饲养的大鼠相比，自我施用乙醇。这所提出的实验的总体目标是确定差异饲养诱导的可塑性是否改变神经元微观结构的完整性，从而影响享乐价值和激励成年期乙醇的显着性。据推测，在营养丰富的环境中饲养雄性和雌性大鼠与抚养男性和女性相比，环境会降低对乙醇的享乐反应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青少年间歇性接触乙醇期间的养育可以改变享乐价值和激励成年期乙醇的显着性。据预测，青少年乙醇暴露期间的富集将防止雄性和雌性大鼠成年后酗酒的风险增加。这拟议的实验将研究青少年乙醇暴露期间的差异抚养方式使用扩散张力成像改变神经元微观结构。据预测，饲养在丰富的环境将防止青春期接触乙醇的有害影响与在孤立或社会条件下饲养的老鼠相比。我们进一步预测性别会改变青少年乙醇暴露对神经元微观结构完整性的影响，因此对女性青春期乙醇对离体大鼠的神经元微观结构造成的损害最大接触。该项目的完成将确定差异化培养会改变激励动机乙醇由于神经元微观结构完整性的改变。该模型的开发将提供我们有能力测试青少年乙醇引起的行为和神经生物学变化暴露在临床前模型系统中，导致可塑性和乙醇产生不同的结果敏感性。