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

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.