DIZOCILPINE (MK-801) INCREASES NOT ONLY DOPAMINE BUT ALSO SEROTONIN AND NOREPINEPHRINE TRANSMISSIONS IN THE NUCLEUS-ACCUMBENS AS MEASURED BY MICRODIALYSIS IN FREELY MOVING RATS

The extracellular concentrations of dopamine (DA), norepinephrine (NE) , and serotonin (5-HT) in the nucleus accumbens (NACC) of freely movin g rats were monitored simultaneously via intracerebral microdialysis. Local infusion of the non-competitive N-methyl-D-aspartate (NMDA) rece ptor antagonist MK-801 (dizocilpine) (5-250 mu M) produced significant increases in extracellular levels of DA, NE and 5-HT in a concentrati on-dependent fashion. Perfusion with tetrodotoxin (TTX, 1 mu M) blocke d the ability of focal MK-801 (50 mu M) to increase DA, NE and 5-HT in the dialysate. Systemic administration of MK-801 (0.3 mg/kg, i.p.) al so produced small, but statistically significant, increases in extrace llular concentrations of DA, NE and 5-HT in the NACC. Our microdialysi s results are consistent with the hypothesis that, in addition to dopa minergic, serotonergic and noradrenergic neurotransmissions in the NAC C are involved in the mechanism by which MK-801 alters behavior in rat s. Also, the present study gives further support to the concept that N MDA receptors within the NACC do not regulate DA release through direc t excitatory control. (C) 1997 Elsevier Science B.V.