ETHANOL DRINKING REDUCES EXTRACELLULAR DOPAMINE LEVELS IN THE POSTERIOR VENTRAL TEGMENTAL AREA OF NONDEPENDENT ALCOHOL-PREFERRING P RATS

Moderate ethanol exposure produces neuroadaptive changes in the mesocorticolimbic dopamine system in nondependent rats, and increases measures of dopamine neuronal activity in vitro and in vivo. Moreover, moderate ethanol drinking and moderate systemic exposure elevates extracellular dopamine levels in mesocorticolimbic projection regions. However, the neuroadaptive changes subsequent to moderate ethanol drinking on basal dopamine levels have not been investigated in the ventral tegmental area (VTA). In the current study, adult female alcohol-preferring (P) rats were divided into alcohol-naïve, alcohol drinking, and alcohol deprived groups. The alcohol drinking group had continuous access to water and ethanol (15%, v/v) for 8 weeks. The alcohol deprived group had 6 weeks of access followed by 2 weeks of ethanol deprivation, 2 weeks of ethanol re-exposure, followed again by 2 weeks of deprivation. The deprived rats demonstrated a robust alcohol deprivation effect upon ethanol reinstatement. The alcohol-naïve group had continuous access to water only. In the last week of the drinking protocol, all rats were implanted with unilateral microdialysis probes aimed at the posterior VTA and no-net-flux microdialysis was conducted to quantify extracellular dopamine levels and dopamine clearance. Results yielded significantly lower basal extracellular dopamine concentrations in the posterior VTA of the alcohol drinking group compared to the alcohol naive and alcohol deprived groups (3.8 ± 0.3 vs. 5.0 ± 0.5 [p < 0.02] and 4.8 ± 0.4 nM, [p < 0.05], respectively). Extraction fractions were significantly (p < 0.0002) different between the alcohol drinking and alcohol naive groups (72 ± 2 vs. 46 ± 4%, respectively) and not significantly different (p = 0.051) between alcohol deprived and alcohol naive groups (61 ± 6% for the alcohol deprived group). The data indicate that reductions in basal DA levels within the posterior VTA occur after moderate chronic ethanol intake in nondependent P rats. This reduction may result, in part, from increased DA uptake and may be important for the maintenance of ethanol drinking. These adaptations normalize with ethanol deprivation and may not contribute to the alcohol deprivation effect.