The study have investigated the effect of a conditioned emotional response using a contextual cue on dopamine release in the rat nucleus accumbens, measured with in vivo microdialysis, and its inhibition by N-methyl-D-aspartate antagonist dizocilpine maleate. The extracellular level of dopamine in the medial nucleus accumbens markedly increased for up to 40 min when rats were given mild footshock in the testing box. When the rats were returned to the testing box, but not given footshock (conditioned emotional response), there was an immediate and long-lasting (80 min) increase in extracellular dopamine. Dizocilpine maleate (50 mumol/l) administered into the nucleus accumbens through the dialysis probe had no significant effect on the immediate increase in dopamine induced by conditioned emotional response but completely prevented the later phase. Dizocilpine maleate had no effect on basal dopamine release in control rats but decreased basal dopamine in rats exposed to footshock 2 h previously. The alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate/kainate antagonist 6-cyano-7-nitroquinnoxaline-2,3-dione (100 mumol/l) had no effect on the increase in dopamine release in response to conditioned emotional response. The results indicate that the acquisition of conditioned emotional response causes long-lasting changes in the mechanisms involved in the glutamatergic control of dopamine release in the nucleus accumbens. Furthermore glutamate inputs into the nucleus accumbens may also regulate the delayed phase of conditioned dopamine release during expression of conditioned emotional response to a contextural cue through activation of N-methyl-D-aspartate receptors.