The extent to which glutamate receptors in the nucleus accumbens and ventral tegmental area regulate feeding-evoked increases in dopamine release in the nucleus accumbens was determined using in vivo brain microdialysis in the rat. In some animals a second dialysis probe was implanted in the ventral tegmental area ipsilateral to the nucleus accumbens probe. The feeding protocol involved access to standard rat chow after 18 h of food deprivation. Under these conditions rats began eating approximately 30 s after the introduction of food and consumed 7-8 g, resulting in a 50% increase in dopamine release. Application of the glutamate receptor antagonist kynurenate (1 mM) in the nucleus accumbens potentiated the feeding-evoked increase in dopamine release by 80%. Application of the metabotropic glutamate receptor agonist trans-1S,3R-1-amino-1,3-cyclopentanedicarboxylic acid (100 microM) in the nucleus accumbens blocked the feeding-evoked increase in dopamine release. Application of a combination of the ionotropic glutamate receptor antagonists 2-amino-5-phosphopentanoic acid (200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) through the dialysis probe in the ventral tegmental area reduced basal dopamine output in the nucleus accumbens by 20% and markedly attenuated (by 70%) the effect of feeding on dopamine release. None of the treatments affected the latency to eat or the volume of food consumed. These results indicate that glutamatergic afferents to the ventral tegmental area mediate feeding-induced increases in dopamine release in the nucleus accumbens. In contrast, at physiological concentrations, glutamate in the nucleus accumbens appears to decrease dopamine release via actions on ionotropic and metabotropic receptors.