Inhibitory effect of reserpine on dopamine transporter function

Previous studies indicate that reserpine may disrupt dopamine transporter activity. Results presented herein reveal that it also inhibits potently synaptosomal [H-3]dopamine uptake. In addition, reserpine administration to rats decreased the V-max of synaptosomal dopamine transport, as assessed ex vivo 12 h after treatment. This decrease appeared, at least in part, dissociated from concurrent inhibition of the vesicular monoamine transporter-2 (VMAT-2). In separate experiments, synaptosomal dopamine uptake did not differ between wild-type and heterozygous VMAT-2 knockout mice, and reserpine treatment did not inhibit [H-3]dopamine uptake into cells heterogously expressing the human dopamine transporter. Taken together, these data suggest that reserpine may transiently alter dopamine transporter function in a noncompetitive, indirect manner. (C) 2002 Published by Elsevier Science B.V.