Ethanol Intake and Reinforcement in Infant Rats

描述（由申请人提供）：最近的证据表明，新生儿和 年龄较大的婴儿大鼠容易消耗乙醇，而无需启动程序（不像 成年人），并把它作为一个食欲抑制剂。建议的实验测试 乙醇的摄入和强化作用。鉴于 流行病学证据表明， 人类婴儿，临床证据表明，产前暴露于乙醇， 人类在青春期预测乙醇滥用，这些实验是相关的， 青少年和成人滥用乙醇以及实验研究， 乙醇的强化作用。第一个具体目标是调查 第二种方法是在婴儿大鼠中自我施用乙醇，第二种方法是测试 乙醇对幼鼠的强化作用这将是完成 对于发育中的大鼠的两个摄取系统中的每一个， 在行为、功能和 神经生理学-吸吮和独立摄入。我们的初步 研究表明，大量摄入乙醇和增强作用， 新生儿的吮吸和较大婴儿的独立摄入。为 乙醇通过哺乳自我管理，最初的实验将 确定乙醇浓度和暴露时间的作用，乙醇 气味独立于其味觉后果，和乙醇风味分离 乙醇？的药理学后果。大致平行的实验是 建议在独立摄入的情况下测试较大的婴儿。的 酒精作为刺激剂（无条件刺激，美国）的有效性将 然后通过巴甫洛夫条件反射测试新生儿， 哺乳期和独立喂养的情况下的老年幼犬。使用两 不同类型的新生儿条件反射，这些测试将评估基本的 决定因素如乙醇浓度和CS-US持续时间 配对和分析问题，如潜在的可分离的加强 乙醇的药理学和味觉属性的后果。相关 问题将在条件反射方面对较大的断奶前仔猪进行测试， 上下文作为CS和摄入乙醇，或其注射（以尽量减少 乙醇的味觉属性），如美国。最后，平行实验 在新生大鼠中测试乙醇的摄入量和强化效果将是 用遗传选择的乙醇摄入量品系（P/NP）的幼鼠进行 HAD/LAD）。了解母亲摄入乙醇的后果 产前和产后早期（母乳喂养）人类暴露于乙醇 可以通过拟议的研究服务，以及 个体发育和摄食的个体发育过程中的神经生理学变化， 在发育中的大鼠中的强化应该有助于揭示神经生理学 控制乙醇的摄入量及其影响，如强化。

DESCRIPTION (provided by applicant): Recent evidence suggests that neonatal and older infant rats readily consume ethanol without initiation procedures (unlike adults) and treat it as an appetitive reinforcer. The proposed experiments test ethanol's ingestion and reinforcing effects throughout infancy. In view of epidemiological evidence for relatively frequent exposure to ethanol among human infants, and clinical evidence that prenatal exposure to ethanol in humans predicts ethanol abuse in adolescence, these experiments are relevant to adolescent and adult abuse of ethanol as well as the experimental study of ethanol's reinforcing effects. The first specific aim is to investigate self-administration of ethanol in infant rats, and the second is to test ethanol's reinforcing effects in infant rats. This will be accomplished separately for each of the developing rat's two systems of ingestion that have been identified and differentiated behaviorally, functionally, and neurophysiologically - suckling and independent ingestion. Our preliminary studies have indicated substantial intake and reinforcing effects of ethanol in both suckling by neonates and independent ingestion by older infants. For ethanol self-administration through suckling, initial experiments would determine the roles of ethanol concentration and duration of exposure, ethanol odor independently of its gustatory consequences, and ethanol flavor separated from ethanol?s pharmacological consequences. Roughly parallel experiments are proposed testing older infants in the context of independent ingestion. The effectiveness of alcohol as a reinforcer (unconditioned stimulus, US) would then be tested for neonates through Pavlovian conditioning in the context of suckling and for older pups in the context of independent feeding. Using two different types of conditioning for neonates, these tests would assess basic determinants such as ethanol concentration and the duration of the CS-US pairing, and analytical issues such as the potentially separable reinforcing consequences of ethanol's pharmacological and gustatory attributes. Related questions will be tested for older preweanlings in terms of conditioning with context as the CS and ingestion of ethanol, or its injection (to minimize gustatory attributes of ethanol), as the US. Finally, parallel experiments testing the intake and reinforcing effects of ethanol in neonatal rats will be conducted with pups from lines genetically selected for ethanol intake (P/NP and HAD/LAD). Understanding of the consequences of maternal ethanol ingestion for prenatal and early postnatal (breastfeeding) human exposure to ethanol could be served by the proposed studies, and correlations between neurophysiological changes during ontogeny and the ontogeny of ingestion and reinforcement in the developing rat should help reveal neurophysiological controls of ethanol intake and its effects such as reinforcement.