1. Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immunochemical/behavioral evidence.
- Author
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Khan AM, Currás MC, Dao J, Jamal FA, Turkowski CA, Goel RK, Gillard ER, Wolfsohn SD, and Stanley BG
- Subjects
- Animals, Behavior, Animal drug effects, Behavior, Animal physiology, Blotting, Western, Excitatory Amino Acid Antagonists pharmacology, Feeding Behavior drug effects, Food Deprivation physiology, Immunohistochemistry, Isomerism, Kainic Acid pharmacology, Male, Piperidines pharmacology, Rats, Rats, Sprague-Dawley, Receptors, N-Methyl-D-Aspartate metabolism, Feeding Behavior physiology, Hypothalamic Area, Lateral metabolism, Receptors, N-Methyl-D-Aspartate physiology
- Abstract
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.
- Published
- 1999
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