title: Orexin A-induced feeding is augmented by caloric challenge.
abstract: Orexin neurons are stimulated by conditions that are glucoprivic, suggesting that orexin signaling may be increased during nutritional duress. We have previously shown that injection of orexin A (OxA) into the rostral lateral hypothalamic area (rLHa) robustly and dose-dependently increases feeding behavior. Thus we hypothesized that exogenous administration of orexin A would induce a greater feeding response after acute food deprivation or perceived caloric duress achieved through 2-deoxyglucose (2DG) administration. To test our hypothesis, male Sprague-Dawley rats implanted with internal guide cannulas directed to the rLHa were exposed to varying degrees of food deprivation (0, 3, 12, 24 h) and 2DG (200 mg/kg) before intra-rLHa OxA (500 pmol) infusion. We also performed a dose-response study using graded doses of OxA (0, 31.25, 125, and 500 pmol) in fed and 24-h fasted rats. OxA administration in conjunction with the highest level of prior food deprivation (24 h) resulted in the greatest feeding response (above baseline means; 0 h deprivation: 1.9 +/- 0.6; 24 h deprivation: 4.4 +/- 0.8; P = 0.0034) and showed a dose-dependent enhancement of feeding. Additionally, 2DG administration before OxA administration resulted in a significantly higher feeding response (above baseline means: 2DG = 1.8 +/- 0.5; OxA = 1.8 +/- 0.4; 2DG + OxA = 5.1 +/- 0.6; P < 0.0001). These data support the hypothesis that orexin signaling may be important in modulating the feeding network under times of nutritional duress.
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Thorpe
authors.forename: J A
authors.initials: JA
authors.lastname: Teske
authors.forename: C M
authors.initials: CM
authors.lastname: Kotz
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D007026:Hypothalamic Area, Lateral; D007267:Injections; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000963:Antimetabolites; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D003847:Deoxyglucose