REDUCED STRIATAL VESICULAR MONOAMINE TRANSPORTERS AFTER NEUROTOXIC BUT NOT AFTER BEHAVIORALLY-SENSITIZING DOSES OF METHAMPHETAMINE

Prior studies indicate long-term reductions of striatal dopaminergic m arkers after sustained, high dose methamphetamine exposures in vivo, s uggesting a neurotoxic effect. We have reported lack of regulation of vesicular monoamine transporter type-2 expression, as opposed to other markers of striatal dopaminergic terminals, under conditions that alt er dopaminergic transmission without synaptic terminal losses. Ln the present study, we evaluated the vesicular monoamine transporter and th e neuronal membrane dopamine transporter in rat striata after in vivo exposure to neurotoxic or to intermittent, low dose (behaviorally-sens itizing, non-neurotoxic) methamphetamine administrations. Vesicular mo noamine transporter binding was measured by autoradiography of (+)-[H- 3]dihydrotetrabenazine, the active isomer of (+/-)-[H-3]dihydrotetrabe nazine. (+)-Dihydrotetrabenazine bound to a homogeneous population of striatal sites in controls with a K-d of 1.5 nM and a B-max of 3.8 fmo l/mu g protein. Neurotoxic methamphetamine treatment reduced both stri atal vesicular monoamine transporter (-26%) and dopamine transporter ( -39%) bindings. There were no changes after the non-neurotoxic treatme nt regimen. The vesicular monoamine transporter may thus be a valuable marker in the further clinical study of psychostimulant drug neurotox icity. (C) 1997 Elsevier Science B.V.