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

• Published in: The American journal of physiology Vol. 270; no. 2; p. R443
• Main Authors: Stanley, B.G. (University of California, Riverside, CA.), Willett, V.L. III, Donias, H.W, Dee, M.G. II, Duva, M.A
• Format: Journal Article
• Language: English
• Published: United States 01.02.1996
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; ACIDE ASPARTIQUE; ACIDE GLUTAMIQUE; ACIDO ASPARTICO; ACIDO GLUTAMICO; AGONISTAS; AGONISTE; ALIMENTACION; ALIMENTATION; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Body Weight - physiology; CEREBRO; CHIMIORECEPTEUR; Circadian Rhythm; COMPORTAMIENTO; COMPORTEMENT; COMPORTEMENT ALIMENTAIRE; Eating - physiology; ENCEPHALE; Excitatory Amino Acid Antagonists - pharmacology; Food Deprivation - physiology; GAIN DE POIDS; GANANCIA DE PESO; Glutamic Acid - physiology; HABITOS ALIMENTARIOS; Hypothalamic Area, Lateral - metabolism; INANICION; INANITION; INGESTION DE ALIMENTOS; Kainic Acid - pharmacology; Male; N-Methylaspartate - pharmacology; PERIODICIDAD; PERIODICITE; PESO; POIDS; PRISE ALIMENTAIRE (HOMME); QUIMIORECEPTORES; RAT; RATA; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - physiology; Time Factors
• ISSN: 0002-9513; 2163-5773
• 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