S04ALCOHOL PROBLEMS IN YOUNG ADULTS TRANSITIONING FROM ADOLESCENCE TO ADULTHOOD: RACE, GENDER AND TRANSLATIONAL FINDINGSS04.1IDENTIFYING SUBSTRATES OF THE NEUROTOXIC EFFECTS OF ETHANOL EXPOSURE DURING ADOLESCENCE IN RATS

Substance abuse typically begins in adolescence; therefore, the impact of alcohol on during this critical time in brain development is of particular importance. Epidemiological data indicate that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences. We have shown that adolescent ethanol exposure via vapor in rats can produce changes in sleep and arousal, impairments in anxiety and affective behavior as well as cortical, hippocampal and basal forebrain neurophysiological function, well into adulthood. However, the neuroanatomical substrates of these effects have yet to be determined. The loss of cholinergic input to the forebrain has been demonstrated following fetal alcohol exposure and in adults with Wernicke-Korsakoff syndrome. In the present study, immunohistochemistry for choline acetyltransferase (ChAT) was determined to assess forebrain cholinergic neurons (Ch1-4), and behavioral deficits following adolescent alcohol exposure. Wistar rats were exposed to ethanol vapor (14 h/on 10 h off/day) for 35 days from P22 to P57 (average BAC 163 mg%). Rats were withdrawn from vapor and assessed for locomotor activity, startle response, conflict behavior in the open field and immobility in the forced swim test as adults. Rats were then sacrificed at Day 72 and perfused for histochemical analyses. Ethanol vapor exposed rats displayed: increased locomotor activity 8 h after the termination of vapor delivery for that 24 h period at Day 10 and 20 of alcohol vapor exposure, significant reductions in the amplitude of their responses to prepulse stimuli during the startle paradigm at 24 h withdrawal, and at 2 weeks following withdrawal, less anxiety-like and/or more 'disinhibitory' behavior in the open field conflict, and more immobility in the forced swim test. Quantitative analyses of ChAT immunoreactivity revealed a significant reduction in cell counts in the Ch1-2 and Ch3-4 regions of the basal forebrain in ethanol vapor exposed rats. This reduction in cell counts was significantly correlated with less anxiety-like and/or more 'disinhibitory' behavior in the open-field conflict test. These studies demonstrate that behavioral measures of arousal, affective state, disinhibitory behavior and ChAT-IR are all significantly impacted by chronic adolescence ethanol exposure and withdrawal in Wistar rats.