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 年龄较大的幼鼠很容易在没有启动程序的情况下摄入酒精(不像 成人)，并将其视为一种食欲增强剂。建议的实验测试 酒精的摄取和强化作用贯穿整个婴儿期。鉴于…… 较频繁接触乙醇的流行病学证据 人类婴儿，和临床证据表明产前接触乙醇在 人类预测青少年会滥用酒精，这些实验与 青少年和成人酒精滥用以及对酒精滥用的实验研究 乙醇的强化作用。第一个具体目标是调查 酒精对幼鼠的自我给药，二是检测 乙醇对幼年大鼠的增强作用。这将会实现的 分别用于发育中的大鼠的两个摄取系统 在行为、功能和行为上进行识别和区分 神经生理学--吮吸和独立摄取。我们的预赛 研究表明，乙醇的大量摄取和增强作用 既有新生儿哺乳，也有较大婴儿独立摄取。为 酒精通过哺乳自我给药，最初的实验将 确定酒精浓度和接触时间的作用 气味独立于其味觉后果，乙醇风味分离 来自乙醇？S的药理后果。大致平行的实验是 建议在独立摄取的情况下测试年龄较大的婴儿。这个 酒精作为增强剂的有效性(无条件刺激，美国) 然后通过巴甫洛夫条件反射对新生儿进行测试 哺乳和年龄较大的幼崽在独立喂养的情况下。使用两个 对于不同类型的新生儿，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，例如潜在的可分离加强 乙醇的药理和味觉属性的后果。相关 将测试年龄较大的预断奶仔猪的条件反射能力 上下文如CS和摄入乙醇，或其注射(以最小化 乙醇的味觉属性)，如美国。最后，平行实验 将测试酒精对新生大鼠的摄入量和增强作用 对来自遗传选择的乙醇摄入量(P/NP)品系的幼崽进行 并拥有/LAD)。了解母亲摄入酒精的后果 对于产前和出生后早期(母乳喂养)人类暴露于酒精 可以被提议的研究所服务，并且之间的相关性 个体发育过程中的神经生理学变化及摄食和 发育中大鼠的强化应有助于揭示神经生理学 酒精摄入量的控制及其强化等作用。

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.