Ethanol induces stronger dopamine release in nucleus accumbens (shell) of alcohol-preferring (bibulous) than in alcohol-avoiding (abstainer) rats

Abstract

Several studies on the differences between ethanol-preferring versus non-preferring rat lines suggest an innate deficit in the mesolimbic dopaminergic system as an underlying factor for ethanol volition. Rats would try to overcome such deficit by engaging in a drug-seeking behaviour, when available, to drink an ethanol solution over water. Thus, in the present study we compared the effect of a single dose of ethanol (1 g/kg, i.p.) on the extracellular levels of monoamines measured by microdialysis in the shell of nucleus accumbens of University of Chile bibulous (UChB) and University of Chile Abstainer (UChA) rats, bred for 79 and 88 generations to prefer or reject ethanol, respectively. It is reported that under basal conditions extracellular dopamine levels are lower in the bibulous than in the abstainer rats, while ethanol induced a 2-fold greater increase of dopamine release in bibulous than in abstainer rats. The greater effect of ethanol in bibulous rats was not associated to differences in blood ethanol levels, since the concentration and elimination of ethanol were virtually identical in both rat lines, indicating that bibulous rats are more sensitive to the stimulation of dopamine release by ethanol than abstainer rats. No differences were observed in 5-hydroxytryptamine or metabolites measured simultaneously under basal or ethanol-stimulating conditions in bibulous and abstainer rats. Overall, the present results suggest that a low dopaminergic tone and a strong mesolimbic dopamine response to ethanol are concerted neurochemical features associated to an ethanol-seeking behaviour in rats.

Figure 1

Effect of systemic saline (1ml/kg, i.p.) or ethanol (1g/kg, i.p.) administration on dopamine release in nucleus accumbens (shell) of ethanol naïve UChA (open triangles and circles for saline and ethanol, respectively) and UChB (filled triangles and circles for saline and ethanol, respectively) monitored by microdialysis in the awake condition. Abscissa: time (min) after saline or ethanol administration. Ordinate: changes in dopamine levels (%) compared to the basal condition (30 min sample immediately before drug administration; arrow). *P<0.05, post hoc comparison. The effect of systemic ethanol on dopamine release was stronger in UChB than in UChA rats, whether on the peak, or on the AUC of the effects were used for the comparisons (two-way F-ANOVA for the effect of ethanol (1,22) = 5.28, P<0.05; F-ANOVA for differences between lines (1,22)= 25.16; P<0.01).