Role of dopamine uptake in NMDA-modulated K⁺-evoked dopamine overflow in rat striatum: An is vivo electrochemical study

An involvement of dopamine uptake in the N-methyl-D-aspartate (NMDA)-modulated dopaminergic transmission in rat striatum was studied using the technique of in vivo electrochemical detection. Microinjection of potassium (K⁺) evoked dopamine overflows from the dopamine-containing nerve terminals in the striatum. While application of NMDA did not evoke any dopamine overflow, co-application of NMDA and K⁺ induced larger dopamine overflows than those by K⁺ alone. Furthermore, dynamic analysis showed that the rate of clearance (T(c)) was reduced by NMDA. Indeed, our uptake study demonstrated an NMDA-induced inhibition of dopamine clearance. The time course of electrochemical signals evoked by microinjection of exogenous dopamine was increased and T(c) was reduced following NMDA application. In order to delineate the effects of NMDA on K⁺-evoked dopamine overflows and/or on dopamine uptake, nomifensine, a dopamine uptake inhibitor was used. Application of nomifensine potentiated K⁺-evoked dopamine overflows. Co-administration of NMDA further augmented dopamine overflows by the K⁺ and nomifensine mixture. Taken together, our data suggest that NMDA concomitantly potentiated dopamine overflows in response to depolarizing stimuli and attenuated dopamine uptake. The increment by NMDA of K⁺-evoked dopamine overflows may partially result from an attenuated dopamine uptake in rat striatum.