MK-801, a non-competitive antagonist of NMDA receptor, prevents methamphetamine-induced decrease of striatal dopamine uptake sites in the rat striatum

Abstract

We investigated the effects of MK-801, a non-competitive antagonist of NMDA receptor, on methamphetamine-induced decrease in dopamine (DA) uptake sites in the rat striatum. Repeated administrations of an escalating dose of methamphetamine (2.5, 5, 7.5. 10 mg/kg s.c. ×2, every other day for a week) produced decreased DA uptake sites assayed by binding with [ 3H]GBR 12935 in the striatum. Co-administration of MK-801 and methamphetamine significantly prevented the methamphetamine-induced decrease in striatal [ 3H]GBR 12935 binding. Administration of MK-801 alone did not affect [ 3H]GBR 12935 binding. These results suggest that some neurochemical effects of methamphetamine may be mediated via mechanism involving excitatory amino acids.