Reduced dopamine release in the nucleus accumbens core of adult rats following adolescent binge alcohol exposure: age and dose-dependent analysis

Abstract

Rationale: Alcohol use in adolescence is one of the most significant predictors of alcohol dependence in adulthood, yet the neurochemical mechanisms underlying this heightened vulnerability remain unknown. Whereas research has focused on characterizing adaptations in the mesolimbic dopamine (DA) system following ethanol exposure in adolescence, whether these changes persist into adulthood has yet to be determined.

Objectives: The objective of this study is to investigate the effects of binge-intermittent ethanol administration in adolescence (P30-50) or early adulthood (P60-80) on DA in the nucleus accumbens (NAc) core after an ethanol challenge in adulthood following a period of abstinence.

Methods: Male Sprague Dawley rats (n = 160) were administered intermittent ethanol injections, 1 or 3 g/kg, intraperitoneally (i.p.) every other day for 20 days starting on either P30 or 60. Following an ethanol-free period of either 7, 14, or 28 days, we measured DA efflux following an ethanol challenge (3 g/kg, i.p.) using electrochemical recording electrodes bilaterally implanted into the NAc core.

Results: Moderate-dose ethanol administration (1 g/kg, i.p.) during adolescence significantly decreased ethanol-evoked DA release in adulthood at 7 and 14 days, but not 28 days, following pretreatment exposure compared to saline controls. Relative to rats pretreated with ethanol in adulthood, moderate-dose ethanol in adolescence significantly reduced DA efflux at all time points measured. Additionally, adult rats pretreated with high dose ethanol administration (3 g/kg, i.p.) displayed significantly decreased DA compared to adolescents after 28 days of withdrawal.

Conclusions: Binge-intermittent ethanol administration during adolescence may induce age-dependent neuroadaptations in the mesolimbic DA system compared to ethanol-treated adults during protracted ethanol withdrawal.

Fig. 1

Representative placements of electrodes within the NAc core. Black shaded area represents outer border of area encompassing all electrodes according to Paxinos and Watson (1997).

Fig. 2

Average DA oxidation current (± SEM) after 3 g/kg (i.p.) ethanol challenge in adult rats pretreated with intermittent saline or ethanol (1 g/kg or 3 g/kg, i.p.) treatments in adolescence (a) or adulthood (b). Symbol (*p<.05) indicates DA current differs significantly from saline pretreatment controls by Dunnett’s post hoc. Group n included within each bar.

Fig. 3

Average DA oxidation current (± SEM) after 3 g/kg ethanol challenge in adult rats pretreated with intermittent saline (a), 1 g/kg (i.p.) ethanol (b) or 3 g/kg ( i.p.) ethanol (c) treatments in adolescence or adulthood. Symbol (*p<.05) indicates DA current significantly differs between age groups at time point. Group n included within each bar.

Fig. 4

Average DA oxidation current response time course to a 3 g/kg ethanol challenge in the 1 g/kg ethanol pretreatment group averaged over challenge time (1, 2 and 4 weeks). Symbol (*p<.05) indicates currents significantly differ at time point by Dunnett’s post hoc.