Alcohol and Cocaine Exposure Modulates ABCB1 and ABCG2 Transporters in Male Alcohol-Preferring Rats

Abstract

Two efflux transporters, ATP-binding cassettes B1 (ABCB1) and G2 (ABCG2), are highly expressed in the endothelial cells of the brain, where they regulate the bioavailability and distribution of several endogenous and xenobiotic compounds. However, whether ABCB1 or ABCG2 has any link with drug dependence, drug withdrawal effects, or the incidence of adverse effects in drug abuser is not known. In this study, we determined the effects of voluntary ethanol consumption following repeated exposure to cocaine or vehicle on the relative mRNA and protein expression of Abcg2/ABCG2 and Abcb1/ABCB1 in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of male alcohol-preferring (P) rats. Male P rats were allowed free choice access to ethanol (15 and 30% v/v) and water for 5 weeks to establish baseline drinking behavior. The following week, rats were either injected with 20 mg/kg i.p. of cocaine or saline, once a day, for 7 days. The relative mRNA and protein expression of Abcb1/ABCB1 and Abcg2/ABCG2 in the NAc and mPFC were significantly decreased in ethanol-saline- and ethanol-cocaine-exposed rats compared to control rats that received neither ethanol nor cocaine. Thus, prolonged exposure to commonly abused drugs, ethanol and cocaine, alters the expression of Abcb1/ABCB1 and Abcg2/ABCG2 mRNA and protein levels in brain areas that play a role in drug dependence.

Keywords: ABCB1; ABCG2; Cocaine; Ethanol; NAc; mPFC.

Fig. 1

The time line for voluntary ethanol drinking and repeated cocaine exposure

Fig. 2

Relative mRNA expression of Abcb1 and Abcg2 in the NAc following voluntary ethanol consumption and repeated cocaine exposure (mean ± SEM). a One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in relative mRNA expression of Abcb1 in the NAc. b One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in relative mRNA expression of Abcg2 in the NAc. (*p < 0.05, **p < 0.01), (n = 5 for each group)

Fig. 3

Relative mRNA expression of Abcb1 and Abcg2 in the mPFC following voluntary ethanol consumption and repeated cocaine exposure (mean ± SEM). a One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in relative mRNA expression of Abcb1 in the mPFC. b One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in relative mRNA expression of Abcg2 in the mPFC. (*p < 0.05, **p < 0.01), (n = 5 for each group)

Fig. 4

ABCB1 and ABCG2 protein expression in the NAc following voluntary ethanol consumption and repeated cocaine exposure (mean ± SEM). a One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in ABCB1 expression in the NAc. b One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in ABCG2 expression in the NAc. (**p < 0.01, ***p < 0.001), (n = 5 for each group)

Fig. 5

ABCB1 and ABCG2 protein expression in the mPFC following voluntary ethanol consumption and repeated cocaine exposure (mean ± SEM). a One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in ABCB1 expression in the mPFC. b One-way ANOVA followed by the Newman-Keuls multiple comparisons test revealed a significant decrease in ABCG2 expression in the mPFC. (*p < 0.05, **p < 0.01,***p < 0.001), (n = 5 for each group)