GLUTAMATE RECEPTORS IN THE NUCLEUS-ACCUMBENS SHELL CONTROL FEEDING-BEHAVIOR VIA THE LATERAL HYPOTHALAMUS

The nucleus accumbens is a brain region considered to be important in the regulation of appetitive behavior and reinforcement. The accumbens receives afferent input from corticolimbic and thalamic structures, w hich is primarily coded by excitatory amino acids (EAAs). The present studies investigated the role of EAA input to the nucleus accumbens in feeding behavior in rats, in two recently characterized subregions of the accumbens, the ''core'' and ''shell.'' In the first series of exp eriments, it was shown that blockade of lpha-amino-3-hydroxy-5-methyli soxazole-4-propionic acid (AMPA) and kainate glutamate receptors in th e medial part of the accumbens, corresponding to the medial shell subr egion, resulted in a pronounced feeding response. Bilateral microinfus ion of 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.25-0.75 mu g/0.5 mu l ), 6-cyano-7-nitroquinoxaline (CNQX, 0.75-1.5 mu g), and 2,3-dihydroxy -6-nitro-7-sulfamoylbenzo-(F) quinoxaline (NBQX, 0.2-1.0 mu g) markedl y stimulated food intake immediately following infusion, in a dose-dep endent manner. Infusion of DNQX into the central accumbens region, cor responding to the core, did not elicit feeding. Infusion of the NMDA a ntagonists 2-amino-5-phosphonopentanoic acid (AP-5) and MK-801 (dizoci lpine maleate) did not elicit feeding in either region. The feeding re sponse to DNQX was blocked by local coinfusion of AMPA. Systemic pretr eatment with naltrexone (5 mg/kg) had no effect on the DNQX-feeding re sponse; however, prior systemic administration of both D-1 and D-2 ant agonists reduced the response by half, suggesting a modulatory role fo r dopamine in the response. Moreover, the feeding response was complet ely inhibited by concurrent infusion of the GABA(A) agonist muscimol ( 10, 25 ng) into the lateral hypothalamus, a major projection area of t he accumbens shell. These findings demonstrate a selective role for no n-NMDA receptors in the nucleus accumbens shell in ingestive behavior, and suggest an important functional link between two major brain regi ons involved in reward, the nucleus accumbens and lateral hypothalamus .