Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 293; no. 3; pp. R1022 - R1026
• Main Authors: Doane, Dolores F, Lawson, Marcus A, Meade, Jonathan R, Kotz, Catherine M, Beverly, J. Lee
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.09.2007
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; Animals; Brain; Diet; Eating - drug effects; Excitatory Amino Acid Antagonists - pharmacology; Hypothalamic Area, Lateral - physiology; Intracellular Signaling Peptides and Proteins - pharmacology; Male; Metabolism; Microdialysis; Microinjections; Neurons; Neuropeptides - pharmacology; Orexins; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - agonists; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Rodents; Sympathomimetics - pharmacology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00282.2007

1 Division of Nutritional Sciences, 2 Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois; and 3 Veterans Affairs Medical Center Geriatric Research Education Clinical Center and Minnesota Obesity Center, Minneapolis, Minnesota Submitted 25 April 2007 ; accepted in final form 30 May 2007 Food intake is stimulated following administration of orexin-A into the perifornical region of the lateral hypothalamus (LH/PFA). Orexin neurons originating in the LH/PFA interact with a number of hypothalamic systems known to influence food intake, including glutamatergic neurons. Glutamatergic systems in the LH/PFA were demonstrated to initiate feeding through N -methyl- D -aspartic acid (NMDA) receptors. Male Sprague-Dawley rats fitted with brain guide cannulas to the LH/PFA were used in two experiments. In the first experiment, a combination microdialysis/microinjection probe was used to deliver artificial cerebrospinal fluid (aCSF) or 500 pmol of orexin-A into the LH/PFA. Orexin-A increased interstitial glutamate to 143 ± 12% of baseline ( P < 0.05), which remained elevated over the 120-min collection period. In the second experiment, the NMDA receptor antagonist D -2-amino-5-phosphonopentanoic acid ( D -AP5; 10 nmol) was administered before orexin-A. The orexin-induced increase in food intake (from 1.1 ± 0.4 to 3.2 ± 0.5 g, P < 0.05) during the first hour was absent in rats receiving D -AP5 + orexin-A (1.2 ± 0.5 g). There was no effect of D -AP5 alone on food intake. These data support glutamatergic systems in the LH/PFA mediating the feeding response to orexin-A through NMDA receptors. food intake regulation; hypocretin; microdialysis Address for reprint requests and other correspondence: J. Lee Beverly, Univ. of Illinois at Urbana-Champaign, 1207 W. Gregory Dr., MC-630, Urbana, IL 61801 (e-mail: beverly1{at}uiuc.edu )