Ethanol potentiates the function of the human dopamine transporter expressed in Xenopus oocytes

Ethanol alters a variety of properties of brain dopaminergic neurons includ ing firing rate, synthesis, release, and metabolism. Recent studies suggest that ethanol's action on central dopamine systems may also involve modulat ion of dopamine transporter (DAT) activity. The human DAT was expressed in Xenopus oocytes to examine directly the effects of ethanol on transporter f unction. [H-3]Dopamine (100 nm) accumulation into DAT-expressing oocytes in creased significantly in response to ethanol (10 min; 10-100 mm). In two-el ectrode voltage-clamp experiments, DAT-mediated currents were also enhanced significantly by ethanol (10-100 mm). The magnitude of the ethanol-induced potentiation of DAT function depended on ethanol exposure time and substra te concentration. Cell surface DAT binding ([H-3]WIN 35,428; 4 nm) also inc reased as a function of ethanol exposure time. Thus, the increase in dopami ne uptake was associated with a parallel increase in the number of DAT mole cules expressed at the cell surface. These experiments demonstrate that DAT -mediated substrate translocation and substrate-associated ionic conductanc es are sensitive to intoxicating concentrations of ethanol and suggest that DAT may represent an important site of action for ethanol's effects on cen tral dopaminergic transmission. A potential mechanism by which ethanol acts to enhance DAT function may involve regulation of DAT expression on the ce ll surface.