Ethanol Intake and Reinforcement in Infant Rats

描述（由申请人提供）：大鼠出生后乙醇摄入和强化的个体发生将在婴儿期早期和青春期进行研究，以确定年龄相关的乙醇反应变化与大脑发育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暴露于乙醇中会增加啮齿动物随后的乙醇摄入和人类滥用乙醇的风险。这种个体发生策略在行为神经科学中有着丰富的历史，为在遗传上选择乙醇敏感性的啮齿动物中测试脑-行为关系的成功策略提供了另一种选择，并且，鉴于有证据表明青春期的特征是促进酒精滥用和酗酒进入成年期的行为，开始测试个体发生进展到青春期这方面是否是突然的，与早期年龄离散的中断。或连续的。第一个具体目的是确定乙醇摄入和乙醇强化在早期婴儿期和青春期之间的大鼠个体发生。具体目标2是验证年龄相关的乙醇摄入特性和婴儿期和青春期之间的强化与脑阿片机制的个体发生变化有关的假设。在许多其他可能对乙醇反应很重要的脑系统中，选择阿片系统进行检查的一个优势是阿片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是测试在早期个体发育的不同阶段暴露于乙醇的动物在青春期的乙醇摄入量，有或没有选择性阿片类拮抗剂。这可能揭示了发育过程中的敏感时期，在这个时期乙醇暴露使个体在以后的酒精滥用中具有特殊的风险，并可能确定早期暴露时的特定阿片类拮抗剂是否会降低青春期酒精摄入增加的可能性。与公共卫生相关的青少年伴随着过量饮酒等行为，可能导致终身酗酒。临床和实验证据表明，过早接触酒精会增加青春期的饮酒量。拟议的实验将追踪出生和青春期之间酒精摄入和强化的年龄相关变化，测试阿片系统的相关影响，并确定青春期之前的潜在敏感期，在此期间酒精暴露尤其会增强青少年的酒精摄入。

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.