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

Am J Physiol. 1999 Mar;276(3):R880-91. doi: 10.1152/ajpregu.1999.276.3.R880.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Blotting, Western
  • Excitatory Amino Acid Antagonists / pharmacology
  • Feeding Behavior / drug effects
  • Feeding Behavior / physiology*
  • Food Deprivation / physiology
  • Hypothalamic Area, Lateral / metabolism*
  • Immunohistochemistry
  • Isomerism
  • Kainic Acid / pharmacology
  • Male
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology*

Substances

  • Excitatory Amino Acid Antagonists
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • ifenprodil
  • Kainic Acid