DIZOCILPINE (MK-801) ELICITS A TETRODOTOXIN-SENSITIVE INCREASE IN EXTRACELLULAR RELEASE OF DOPAMINE IN RAT MEDIAL FRONTAL-CORTEX

We have examined in the rat the effects of a selective non-competitive antagonist for the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor, dizocilpine (MK-801), on cortical dopamine (DA) metabol ism using an in vivo dialysis technique. An acute intraperitoneal inje ction of MK-801 (0.4-1.25 mg/kg;) dramatically increased the concentra tions of dopamine, 3,4-dihydroxy-phenylacetic acid and homovanillic ac id in the dialysates from the medial frontal cortex in a dose-dependen t fashion. Moreover, MK-801 caused a delayed and small augmentation of the cortical extracellular release of 5-hydroxyindoleacetic acid. Con tinuous infusion of tetrodotoxin into the prefrontal region via the mi crodialysis tube completely blocked the ability of MK-801 (1.25 mg/kg, intraperitoneally) to augment the extracellular release of DA, its me tabolites and the serotonin metabolite in the frontal cortex. The pres ent results suggest that MK-801 Facilitates DA release in the medial f rontal cortex by increasing impulse Row in the DA neurons projecting t o the cortical area, adding further support to the view that the NMDA receptor may be involved in the tonic inhibition of frontal cortical D A neurons. II is also proposed that frontal serotonin neurons might be under regulation by excitatory amino acidergic transmission via the N MDA receptor.