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Am J Physiol Regul Integr Comp Physiol 293: R1022-R1026, 2007. First published May 30, 2007; doi:10.1152/ajpregu.00282.2007
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

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

Dolores F. Doane,1 Marcus A. Lawson,2 Jonathan R. Meade,2 Catherine M. Kotz,3 and J. Lee Beverly1,2

1Division of Nutritional Sciences, 2Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois; and 3Veterans 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)






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