In the present study, we examined the effect of amantadine on extracellular dopamine levels in the rat striatum using an in vivo microdialysis. Perfusion of amantadine (0.1-1 mM) through the microdialysis probe caused an increase both in extracellular dopamine and glutamate levels in rat striatum. Amantadine was found to increase extracellular dopamine concentration in Ca(2+)-dependent manner, but the effect was not abolished by omega-conotoxin. Although intraperitoneal administration of MK-801 [(+)-5-methyl-10, 11-dihydroxy-5H-dibenzo (a,d)cyclohepten-5,10-imine] alone could not significantly alter the concentration of dopamine, it attenuated amantadine-induced increase in dopamine level. These findings suggest that an interaction between dopaminergic and glutamatergic neurotransmission is an important component in the regulation of striatal dopamine levels.