Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immunochemical/behavioral evidence

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 276; no. 3; pp. 880 - R891
• Main Authors: Khan, A.M. (University of California, Riverside.), Curras, M.C, Dao, J, Jamal, F.A, Turkowski, C.A, Goel, R.K, Gillard, E.R, Wolfsohn, S.D, Stanley, B.G
• Format: Journal Article
• Language: English
• Published: United States 01.03.1999
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Blotting, Western; BRAIN; CEREBRO; COMPORTEMENT ALIMENTAIRE; ENCEPHALE; Excitatory Amino Acid Antagonists - pharmacology; Feeding Behavior - drug effects; Feeding Behavior - physiology; FEEDING HABITS; Food Deprivation - physiology; HABITOS ALIMENTARIOS; Hypothalamic Area, Lateral - metabolism; HYPOTHALAMUS; Immunohistochemistry; Isomerism; Kainic Acid - pharmacology; Male; N-METHYL-D-ASPARTATE; Piperidines - pharmacology; RAT; RATA; RATS; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - metabolism; Receptors, N-Methyl-D-Aspartate - physiology
• ISSN: 0002-9513; 0363-6119; 2163-5773; 1522-1490
• DOI: 10.1152/ajpregu.1999.276.3.R880

1  Division of Biomedical Sciences, and Departments of 2  Neuroscience and 3  Psychology, University of California, Riverside, California 92521 Cells within the lateral hypothalamic area (LHA) are important in eating control. Glutamate or its analogs, kainic acid (KA) and N -methyl- D -aspartate (NMDA), elicit intense eating when microinjected there, and, conversely, LHA-administered NMDA receptor antagonists suppress deprivation- and NMDA-elicited eating. The subunit composition of LHA NMDA receptors (NMDA-Rs) mediating feeding, however, has not yet been determined. Identifying this is important, because distinct second messengers/modulators may be activated by NMDA-Rs with differing compositions. To begin to address this, we detected LHA NR2A and NR2B subunits by immunoblotting and NR2B subunits by immunohistochemistry using subunit-specific antibodies. To help determine whether NMDA-Rs mediating feeding might contain these subunits, we conducted behavioral studies using LHA-administered ifenprodil, an antagonist selective for NR2A- and/or NR2B-containing NMDA-Rs at the doses we used (0.001-100 nmol). Ifenprodil maximally suppressed NMDA- and deprivation-elicited feeding by 63 and 39%, respectively, but failed to suppress KA-elicited eating, suggesting its actions were behaviorally specific. Collectively, these results suggest that LHA NMDA-Rs, some of which contribute to feeding control, are composed of NR2A and/or NR2B subunits, and implicate NR2A- and/or NR2B-linked signal transduction in feeding behavior. glutamate; ifenprodil; microliter injections; immunoblotting; immunohistochemistry; N -methyl- D -aspartate