The extracellular concentrations of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in the nucleus accumbens (NACC) of freely moving rats were monitored simultaneously via intracerebral microdialysis. Local infusion of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) (5-250 microM) produced significant increases in extracellular levels of DA, NE and 5-HT in a concentration-dependent fashion. Perfusion with tetrodotoxin (TTX, 1 microM) blocked the ability of focal MK-801 (50 microM) to increase DA, NE and 5-HT in the dialysate. Systemic administration of MK-801 (0.3 mg/kg, i.p.) also produced small, but statistically significant, increases in extracellular concentrations of DA, NE and 5-HT in the NACC. Our microdialysis results are consistent with the hypothesis that, in addition to dopaminergic, serotonergic and noradrenergic neurotransmissions in the NACC are involved in the mechanism by which MK-801 alters behavior in rats. Also, the present study gives further support to the concept that NMDA receptors within the NACC do not regulate DA release through direct excitatory control.