Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control

Am J Physiol. 1996 Feb;270(2 Pt 2):R443-9. doi: 10.1152/ajpregu.1996.270.2.R443.


To determine whether endogenous lateral hypothalamic (LH) glutamate and its N-methyl-D-aspartate (NMDA) receptors might participate in the stimulation of natural eating, LH injection of the NMDA antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) was tested in adult male rats for suppressive actions on feeding elicited by 1) NMDA, kainic acid or D, L-alpha-amino-3-hydroxy-5-methylisoxazole (AMPA) injected into the LH; 2) food deprivation; and 3) the onset of the nocturnal period. D-AP5 (10-100 nmol) reduced by 72-90% the approximately 10-g eating response elicited by NMDA (10 nmol) without affecting the quantitatively similar eating responses elicited by kainic acid (1.0 nmol) or AMPA (1.0 nmol). This treatment also suppressed deprivation-induced eating by as much as 61% and nocturnal eating by as much as 40%. To determine its long-term effects, D-AP5 (50 nmol) was injected bilaterally into the LH twice a day for 8 consecutive days. This treatment caused up to 65% reductions in daily food intake and body weight loss of up to 13 g/day. These findings, showing behaviorally selective suppressions of eating and body weight by D-AP5, argue that endogenous LH glutamate acts to regulate natural eating and body weight and that NMDA receptors participate in these functions.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Animals
  • Body Weight / physiology*
  • Circadian Rhythm
  • Eating / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Food Deprivation / physiology
  • Glutamic Acid / physiology*
  • Hypothalamic Area, Lateral / metabolism*
  • Kainic Acid / pharmacology
  • Male
  • N-Methylaspartate / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Time Factors
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • N-Methylaspartate
  • 2-Amino-5-phosphonovalerate
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Kainic Acid