Evidence for involvement of N-methyl-D-aspartate receptor in tonic inhibitory control of dopaminergic transmission in rat medial frontal cortex

Bilateral infusion of DL-2-amino-5-phosphonovalerate (DL-APV) (which is a competitive antagonist for N-methyl-D-aspartate (NMDA) receptor) into the medial frontal cortex of conscious rats increased the amount of 3,4-dihydroxyphenylacetic acid (DOPAC) and the DOPAC/dopamine (DA) ratio in the cortical area. Moreover, intra-prefrontal injection of DL-APV, D-APV, DL-2-amino-7-phosphonoheptanoate and 3-[(+/-])-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (which are selective NMDA receptor antagonists), but not the L-isomer of APV and gamma-glutamyl-aminomethyl sulphonate (a relative antagonist for non-NMDA receptors), facilitated prefrontal DA utilization in a NMDA-reversible manner. These findings suggest that NMDA-type excitatory amino acid receptors may be involved in a tonic inhibitory regulation of dopaminergic transmission in the medial frontal cortex in vivo.