NMDA receptors are not involved in the MK-801-induced increase of striatal dopamine release in rat: a microdialysis study.

Brain microdialysis and high-performance liquid chromatography with electrochemical detection were utilized to study the effect of the selective non-competitive NMDA antagonist MK-801 (dizocilpine) on striatal dopamine (DA) release in the anesthetized rat. Perfusion of 100 microM and 300 microM (+/-)-MK-801 through the probe did not significantly change the basal release of DA. These results suggest that excitatory amino acids do not exert a tonic excitatory influence on striatal DA release through NMDA receptors. 1 mM and 3 mM (+/-)-MK-801 caused a significant increase (398% and 580%, respectively), while there was no change in the level of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). To clarify the mechanism of the (+/-)-MK-801-induced increase, the differential effect of its enantiomers (the active (+)-MK-801 and the less active (-)-MK-801) was determined. There was no difference in the action of these compounds: both drugs increased the striatal DA release with the same efficacy. Our data suggest that the MK-801-induced increase of striatal DA release is not an NMDA receptor-mediated effect.