Neurochemical characteristics associated with ethanol preference in selected alcohol-preferring and -nonpreferring rats: a quantitative microdialysis study.
BACKGROUND
Rodent lines selected for alcohol preference and nonpreference have been used extensively to determine the neurobiological basis of alcohol-seeking behavior. Evidence suggests that innate differences in the mesolimbic dopamine and serotonin systems may contribute to disparate alcohol-seeking behaviors between these selected lines. Therefore, the purpose of this study was to identify neurochemical characteristics which may predict ethanol 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 subsequent measures of ethanol preference. Initially, basal extracellular DA and 5-HT levels were measured by "no-net-flux" quantitative microdialysis. Subsequently, the dopaminergic response to systemic ethanol administration (1.5 g/kg; intraperitoneal) was determined. After completion of the neurochemical 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 extracellular dopamine levels ([DA]e; r = + 0.64;p < 0.006) and the percent of baseline increase in DA (%incrDA; r = + 0.77;p < 0.001) due to ethanol were significant predictors of ethanol preference. Comparison of the data between genetic lines yielded a significant relationship between preference and %incrDA (r = + 0.87; p < 0.05). Analysis of the data across animals within each line and their respective control line determined that in the AA/ANA line 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, %incrDA (r = + 0.56; p < 0.005) and [DA]e (r = + 0.86; p < 0.004) were significant predictors of ethanol preference.


CONCLUSIONS
Overall, these findings suggest that elevated extracellular levels of dopamine within the nucleus accumbens and a greater responsivity to enhancements in DA release by ethanol may be factors which contribute to high-alcohol preference. Furthermore, the data suggest that alcohol may be more reinforcing in animals that exhibit an enhanced dopaminergic response to the first ethanol exposure, and that this effect may subsequently be associated with high-alcohol-seeking behavior.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA. skatner@yahoo.com
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D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D005518:Food Preferences; D008297:Male; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity
D012701:Serotonin; D000431:Ethanol; D004298:Dopamine