Ethanol Intake and Reinforcement in Infant Rats

描述（由申请方提供）：将在婴儿早期和青春期之间研究大鼠乙醇摄入和强化的出生后个体发育，以确定响应乙醇的年龄相关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会增加啮齿动物随后的乙醇摄入量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具有丰富的历史，为测试遗传选择的乙醇敏感性啮齿动物的大脑-行为关系的成功策略提供了替代方案，并且，鉴于青春期的特征是促进酒精滥用和酒精中毒进入成年期的行为的证据，开始测试进入青春期这方面的个体发生进展是否突然，从早期的离散中断，或连续。第一个具体的目的是确定乙醇摄入和乙醇强化的大鼠在婴儿早期和青春期之间的个体发育。具体目标2是测试的假设，即年龄相关的特殊性，乙醇摄入和强化之间的婴儿早期和青春期与脑阿片类药物机制的个体发生变化。在对乙醇反应可能重要的许多其他脑系统中，选择阿片系统进行检查的一个优点是阿片拮抗剂纳洛酮在治疗酒精滥用中的广泛临床应用。具体目标3是测试在个体发育早期的不同阶段暴露于乙醇的动物在青春期的乙醇摄入，有或没有选择性阿片类拮抗剂。这可能揭示了敏感时期的发展过程中，乙醇暴露的地方，个人在以后的乙醇滥用的特殊风险，并可能决定是否特定的阿片类药物拮抗剂在早期暴露的时间减少的可能性，提高乙醇摄入在青春期。青少年伴随着诸如过量饮酒等行为，这些行为可能导致终身酗酒。临床和实验证据表明，早期接触酒精会增加青春期的摄入量。拟议的实验将跟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对酒精的摄入。

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.