The corticostriatal pathway is believed to utilize the excitatory amino acid glutamate as its transmitter, and the striatum contains high levels of all glutamate receptor subtypes. It has recently been demonstrated that blockade of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate glutamate receptors in the medial part of the accumbens, corresponding to the medial shell subregion, results in a pronounced feeding response. In order to more precisely localize this response, a microinfusion mapping study was conducted. Bilateral microinfusions of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0, 50, 250, 750 ng/0.5 microl), an antagonist that blocks AMPA and kainate receptors, were carried out in eight striatal subregions in different groups of animals. In non-deprived rats, food intake (normal chow), feeding duration, and several other behavioral measures were assessed during a 30 min test session. DNQX significantly and potently enhanced food intake when injected into the accumbens shell, but not into any other region examined, including accumbens core, anterior dorsal, posterior dorsal, ventromedial, dorsomedial, and ventrolateral striatum. The most sensitive site within the accumbens was found to be the posterior aspects of the shell, in which the lowest dose (50 ng DNQX) augmented feeding. These results suggest that a circumscribed region within the nucleus accumbens has a unique role in the control of feeding. It is postulated that removal of tonic excitatory inputs to this region with DNQX results in disinhibition of brain circuits critical for ingestive behavior.