Sex differences in mesolimbic dopamine responses to ethanol and relationship to ethanol intake in rats

Sex differences in ethanol intake in rats suggest that there may be sex differences in brain dopamine systems believed to mediate ethanol's reinforcing properties. To test this hypothesis, we used in vivo microdialysis to examine changes in nucleus accumbens and striatal dopamine, DOPAC and HVA following acute administration of several doses of ethanol in male and female Long-Evans rats. Following dialysis, rats were trained to bar press for oral ethanol reinforcement. In nucleus accumbens, females showed greater increases in dopamine than males at low to intermediate doses. In striatum, both sexes showed increased dopamine at the low to intermediate doses. In addition to showing increased responsiveness to ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol than males during behavioral testing. Correlations between neurochemical measures and subsequent ethanol consumption indicated that among males, both basal and peak ethanol-induced nucleus accumbens dopamine levels were inversely related to later ethanol intake. No such relationship was observed for females. Striatal neurochemical measures were not significantly related to ethanol intake. These findings supported the hypothesis of sex differences in mesolimbic responses to ethanol and suggested that the relationship of those responses to subsequent ethanol intake may differ for males and females.