Inhibitory effect of MK-801 on amantadine-induced dopamine release in the rat striatum.

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.