Adolescent alcohol abuse is a significant health concern. However, the long term consequences of adolescent alcohol exposure in animal models have not been extensively examined. Studies from this laboratory demonstrate impaired cortical, hippocampal, and basal forebrain function in adult rats exposed to alcohol during adolescence. These neurophysiological deficits point towards deficits in attention and memory function which may model those observed in adolescent alcohol abusers . Adolescent N-methyl-D-asparate (NMDA) receptor systems are likely to play a key role in ethanol’s unique effects on the adolescent due to their increased sensitivity to ethanol. NMDA receptors also play an important role in the regulation of attention and memory function in brain regions demonstrated to be impaired by adolescent alcohol exposure. The principal hypothesis underlying this proposal is: Ethanol exerts its unique effects on the adolescent by inducing a lasting upregulation of NMDA systems. As a consequence, the development of ethanol withdrawal and neurodegeneration is enhanced in adolescents. Furthermore, this NMDA upregulation persists into adulthood and contributes to the long term neurophysiological and cognitive deficits observed following adolescent alcohol exposure. The studies proposed in this application examine the development of ethanol dependence and the lasting neurobehavioral consequences of adolescent ethanol exposure using behavioral, cellular/histochemical, and neurophysiological techniques. The goals of this application are accomplished through the following specific aims:
AIM 1. To investigate the development of ethanol dependence during adolescence.
AIM 2. To investigate the behavioral consequences of adolescent ethanol exposure, with a focus on sustained attention and working memory.
AIM 3: To investigate the neurochemical substrates underlying the lasting neurobehavioral consequences of adolescent ethanol exposure, with a focus on NMDA systems.