The overall objectives of this proposal are to determine, using rodent models, neurobiological and behavioral factors involved in promoting high alcohol drinking in adolescent, and some long range consequences of adolescent alcohol drinking. The hypotheses to be tested are (l)-neurobiological and behavioral factors associated with excessive alcohol drinking in adults are also present during adolescence; (2) the acquisition of alcohol drinking during adolescence can be influenced by pharmacological treatments; and (3) chronic alcohol drinking during adolescence produces long-range neurobiological and behavioral consequences in adulthood. These hypotheses will be tested using lines of rats selectively bred for high or low alcohol drinking behavior. Autoradiography procedures, using labeled ligands for the serotonin (5-HT) and dopamine (DA) transporters, will be used to assess differences in adolescent and adult rats with a family history positive (FHP) for alcohol drinking, i.e., alcohol-preferring P and high alcohol-drinking HAD lines, or a family history negative (FHN) for alcohol drinking, i.e., alcohol-nonpreferring NP and low alcohol-drinking LAD rats. Local cerebral glucose utilization (LCGU), as measured by [14C]-2-deoxyglucose (2-DG) uptake and quantitative autoradiography, will be used to determine innate regional differences in functional activity, and the effects of low to moderate doses of ethanol on this activity. Pharmacological challenge studies will examine the response to 5-HT and DA agents in the startle reflex response test. Behavioral studies will be undertaken to evaluate the effects of low to moderate doses of ethanol on prepulse inhibition, and performance on the oscillating bar task. Pharmacological treatment during adolescence with 5-HT3 and opioid antagonists will determine if the acquisition of alcohol drinking can be reduced or prevented in FHP rats. Long-range consequences of adolescent alcohol drinking will be assessed with the ['4 C]-2-DG procedure, and with behavioral measures of spatial navigation Teaming, attention, and motor responses to alcohol. Key findings will be assessed in both male and female rats. Information gained from this proposal will help bridge the gap between human and basic animal research, provide better insight into factors promoting adolescent alcohol drinking, and identify some long-range effects of early alcohol drinking on CNS function.
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