Neurochemical characteristics associated with ethanol preference in selected alcohol-preferring and -nonpreferring rats: A quantitative microdialysisstudy

Background: Rodent lines selected for alcohol preference and nonpreference have bean used extensively to determine the neurobiological basis of alcoho l-seeking behavior. Evidence suggests that innate differences in the mesoli mbic dopamine and serotonin systems may contribute to disparate alcohol-see king behaviors between these selected lines. Therefore, the purpose of this study was to identify neurochemical characteristics which may predict etha nol preference in selected alcohol-preferring and -nonpreferring rats [high -alcohol-preferring (HAD), low-alcohol-preferring (LAD), Alko alcohol (AA), Alko nonalcohol (ANA), Wistar]. Methods: Basal release of dopamine (DA) and serotonin (5-HT) in the nucleus accumbens of ethanol-naive rats was analyzed for its relationship with sub sequent measures of ethanol preference. initially, basal extracellular DA a nd 5-HT levels were measured by "no-net-flux" quantitative microdialysis. S ubsequently, the dopaminergic response to systemic ethanol administration ( 1.5 g/kg; intraperitoneal) was determined. After completion of the neuroche mical tests, the rats received unlimited two-bottle, free-choice access to 10% (w/v) ethanol and water in the home cage for 28 days. Results: Analysis of the data across individual animals revealed that extra cellular dopamine levels ([DA]e; r = + 0.64;p < 0.006) and the percent of b aseline increase in DA (%incrDA; r = + 0.77;p < 0.001) due to ethanol were significant predictors of ethanol preference. Comparison of the data betwee n genetic lines yielded a significant relationship between preference and % incrDA (r = + 0.87; p < 0.05). Analysis of the data across animals within e ach line and their respective control line determined that in the AA/ANA li ne pair (r = + 0.67;p < 0.03) and Wistar line (r = + 0.66;p < 0.03) %incrDA was a significant predictor of preference. In the HAD/LAD line pair, %incr DA (r = + 0.56; p < 0.005) and [DA]e (r = + 0.86;p < 0.004) were significan t predictors of ethanol preference. Conclusions: Overall, these findings suggest that elevated extracellular le vels of dopamine within the nucleus accumbens and a greater responsivity to enhancements in DA release by ethanol may be factors which contribute to h igh-alcohol preference. Furthermore, the data suggest that alcohol may be m ore reinforcing in animals that exhibit an enhanced dopaminergic response t o the first ethanol exposure, and that this effect may subsequently be asso ciated with high-alcohol-seeking behavior.