Role of dopamine in behavioral sensitization to ethanol in DBA/2J mice

Behavioral sensitization has been proposed to play an important role in addiction. Elucidation of the neural processes mediating sensitization may therefore lead to the development of new pharmacotherapeutic treatments. A large number of studies have examined sensitization to psychostimulants and morphine. In contrast, despite the prevalence of alcoholism, the neural processes underlying sensitization to ethanol have not been identified. The aim of the present study was to examine the role of different components of the dopamine system in sensitization to the locomotor stimulant effects of ethanol in DBA/2J mice. Sensitization was induced by administering ethanol [2 g/kg intraperitoneally (ip)] before locomotor activity trials. Control groups received saline (12.5 ml/kg ip) before each activity trial. The ability of the dopamine uptake inhibitors GBR 12909 (3.33-10.0 mg/kg) and bupropion (20 and 30 mg/kg) to cross-sensitize to ethanol was then examined. In addition, the effects of SKF 82958 (0.1-1.0 mg/kg), a dopamine D(1) (D(1)) receptor agonist, quinpirole (0.05 and 0.1 mg/kg), a dopamine D(2)/D(3) (D(2)/D(3)) receptor agonist, and a combination of SKF 82958 and quinpirole were examined. Cross-sensitization was observed between the dopamine uptake inhibitor GBR 12909 and ethanol. In contrast, the less selective uptake inhibitor bupropion did not exhibit cross-sensitization. Similarly, stimulation of D(1) and D(2)/D(3) receptors did not cause cross-sensitization even when the agonists were administered together. Taken together, these data suggest that sensitization to ethanol is associated with changes in the dopaminergic system.