REGIONAL EFFECTS OF MK-801 ON DOPAMINE RELEASE - EFFECTS OF COMPETITIVE NMDA OR 5-HT2A RECEPTOR BLOCKADE

The open channel N-methyl-D-aspartate (NMDA) receptor antagonists dizo cilpine (MK-801) and phencyclidine (PCP) increase the firing rate of b oth A9 and Al0 dopaminergic neurons in the rat. In the Al0 nucleus, th is effect of MK-801 is reportedly prevented by either competitive NMDA antagonists or serotonin(2) (5-HT2) antagonists. The present study ex amined the neurochemical correlates of these effects using the techniq ue of in vivo microdialysis in conscious rats. In contrast to its repo rted electrophysiological effects at the cell body level, MK-801 (2 mg /kg, i.p.) has divergent effects on dopamine release in the terminal f ields of the A9 and A10 systems. MK-801 stimulated dopamine release in both the medial prefrontal cortex and the nucleus accumbens but tende d to decrease release in the striatum. Stimulated dopamine release in the nucleus accumbens was selectively blocked by either the competitiv e NMDA receptor antagonist, MDL 100,453 or the 5-HT2A receptor antagon ist, MDL 100,907. Neither MDL 100,453 nor MDL 100,907 affected MK-801- induced release in the medial prefrontal cortex. The results illustrat e the complex regulation of the forebrain dopaminergic systems by glut amate and indicate that the serotonergic system, via the 5-HT2A recept or, may play an important role in this regulation.