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

Dolores F. Doane, Marcus A. Lawson, Jonathan R. Meade, Catherine M. Kotz, J. Lee Beverly

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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.

Original languageEnglish (US)
Pages (from-to)R1022-R1026
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3
StatePublished - Sep 2007


  • Food intake regulation
  • Hypocretin
  • Microdialysis


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