Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus.
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.
Doane
Dolores F
DF
University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801, USA.
Lawson
Marcus A
MA
Meade
Jonathan R
JR
Kotz
Catherine M
CM
Beverly
J Lee
JL
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004435:Eating / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000037:antagonists & inhibitors; D013566:Sympathomimetics / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016194:Receptors, N-Methyl-D-Aspartate; D013566:Sympathomimetics; D015763:2-Amino-5-phosphonovalerate