Ethanol Intake and Reinforcement in Infant Rats

描述(由申请人提供)：将在早期婴儿期和青春期对大鼠酒精摄入和强化的出生后个体发生进行研究，以确定与年龄相关的对酒精的反应变化与大脑发育的相应变化之间的关系。这种关系可能有助于解释为什么胎儿或婴儿适度接触乙醇会增加啮齿动物随后的乙醇摄入量，并增加人类滥用乙醇的风险。这种个体发育策略在行为神经科学领域有着卓有成效的历史，它提供了一种替代成功的策略，即测试通过遗传方式选择的酒精敏感性啮齿动物的大脑行为关系，鉴于有证据表明，青春期的特征是促使酗酒和酗酒进入成年期的行为，开始测试个体发育进入青春期的这一方面是突然的、与早期年龄的离散中断还是连续的。第一个具体目标是确定大鼠在婴儿期和青春期的酒精摄入和酒精强化的个体发育。具体目标2是测试这一假说，即在婴儿期和青春期早期与年龄相关的酒精摄取和强化的特性与大脑阿片类药物机制的个体发育变化有关。在对酒精反应可能很重要的许多其他大脑系统中，选择阿片系统进行检查的一个优势是阿片类拮抗剂纳曲酮在治疗酒精滥用方面的广泛临床应用。具体目标3是测试在个体发育早期不同阶段接触过乙醇的动物在青春期期间的乙醇摄入量，无论是否使用选择性阿片类拮抗剂。这可能揭示发育期间的敏感期，在这一时期，乙醇暴露使个人面临以后乙醇滥用的特别风险，并可能确定在早期暴露时特定的阿片类拮抗剂是否降低了青春期酒精摄入量增加的可能性。与公共健康相关的青春期伴随着过度饮酒等行为，有可能终身酗酒。临床和实验证据表明，早期接触酒精会增加青春期酒精的摄入量。拟议的实验将跟踪出生到青春期之间酒精摄取和强化的年龄相关变化，测试阿片系统的相关影响，并确定青春期前的潜在敏感期，在这一时期，酒精暴露特别增加青少年的酒精摄入量。

DESCRIPTION (provided by applicant): Postnatal ontogeny of ethanol ingestion and reinforcement in the rat will be studied between early infancy and adolescence toward determining the relationship between age-related changes in response to ethanol and corresponding changes in brain development. This relationship may help explain why modest exposure of fetus or infant to ethanol increases subsequent ethanol ingestion among rodents and risk for ethanol abuse in humans. Such an ontogenetic strategy has a productive history in behavioral neuroscience, provides an alternative to the successful strategy of testing brain- behavior relationships in rodents selected genetically for ethanol sensitivity, and, in view of evidence that adolescence is characterized by behaviors that promote alcohol abuse and alcoholism into adulthood, begins tests of whether ontogenetic progression into this aspect of adolescence is abrupt, a discrete break from earlier ages, or continuous. The first specific aim is to determine the ontogeny of ethanol ingestion and ethanol reinforcement in the rat between early infancy and adolescence. Specific Aim 2 is to test the hypothesis that age-related peculiarities of ethanol ingestion and reinforcement between early infancy and adolescence are associated with ontogenetic change in brain opioid mechanisms. Among many other brain systems likely important for response to ethanol, one advantage of selecting the opioid systems for examination is the widespread clinical application of the opioid antagonist, naltrexone, in treatment of alcohol abuse. Specific Aim 3 is to test ethanol ingestion during adolescence for animals that have been exposed to ethanol at different stages of earlier ontogeny, with or without a selective opioid antagonist. This may reveal sensitive periods during development at which ethanol exposure places the individual at special risk for later ethanol abuse, and may determine whether specific opioid antagonists at the time of early exposure decrease the likelihood of enhanced ethanol ingestion during adolescence. PUBLIC HEALTH RELEVANCE Adolescence is accompanied by behaviors such as excessive alcohol ingestion that risk life-long alcohol abuse. Clinical and experimental evidence indicates that earlier exposure to alcohol increases its ingestion in adolescence. Proposed experiments will track age-related change in alcohol ingestion and reinforcement between birth and adolescence, test associated influence of the opioid system, and determine potential sensitive periods prior to adolescence at which exposure to alcohol especially enhances adolescent ingestion of alcohol.