Adolescent alcohol drinking is a major problem in the U.S. and many other countries. Neurobiological factors that contribute to early onset of alcohol drinking and the long-range consequences of adolescence alcohol drinking are poorly understood. The goals of this project are to determine the enduring effects of adolescent alcohol drinking on (a) behavioral measures of alcohol -seeking and -drinking behaviors in adulthood;(b) neurobiological measures of the function of the mesolimbic dopamine (DA) system;and (c) behavioral measures of the aversive and motor-impairing effects of ethanol (EtOH). The overall hypothesis to be tested is that access to ethanol (EtOH) by adolescents with a genetic predisposition for high alcohol-drinking behavior, i.e., family history positive (FHP) for alcoholism, produces enduring alterations in neural circuits mediating alcohol -seeking and -drinking behaviors. This hypothesis will be tested using rat lines selectively bred for high alcohol intake, i.e., the alcohol-preferring (P) and high-alcohol-drinking (HAD) lines. These lines readily initiate high alcohol drinking during peri-adolescence and attain adult levels of EtOH intake within a short period.
Aim 1 will use operant procedures to measure the effects of continuous and intermittent (binge-like drinking) peri-adolescent alcohol drinking on acquisition of EtOH self-administration, alcohol-seeking behavior (responding in the absence of EtOH reinforcement), and relapse (responding for EtOH after a period of abstinence).
Aim 2 will use the intra-cranial self-administration technique to determine the effects of peri-adolescent alcohol drinking on the reinforcing effects of EtOH within the posterior ventral tegmental area (VTA) of adult rats.
Aim 3 will use quantitative microdialysis (i.e., the no-net-flux method) to determine the enduring effects of peri-adolescent alcohol drinking on DA release and clearance within the nucleus accumbens (ACB) shell and ventral pallidum (VP).
Aim 4 will examine the consequences of peri-adolescent alcohol drinking on the threshold to the aversive effects of EtOH (as measured by conditioned taste aversion), and response to the motor impairing effects of EtOH (as measured in the oscillating bar task) in adulthood. Overall, the results of this project will provide important behavioral and neurobiological information on the long-range consequences of early age onset of alcohol drinking by FHP subjects. Such information could be helpful in developing useful strategies for combating the major problem of adolescent alcohol drinking.
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