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1 Neuroscience, University of Minnesota, Minneapolis, MN, USA
2 Food Science and Nutrition, University of Minnesota, Minneapolis, MN, USA
3 Neuroscience, University of Minnesota, Minneapolis, MN, USA; The Minnesota Obesity Center, University of Minnesota, Minneapolis, MN, USA; GRECC (11G), Veterans Affairs Medical Center, Minneapolis, MN, USA
* To whom correspondence should be addressed. E-mail: kotzx004{at}umn.edu.
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 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 following 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 cannulae directed to the rLHa, were exposed to varying degrees of food deprivation (0, 3, 12, 24 h) and 2DG (200mg/kg) prior to intra-rLHa orexin A (500 pmol) infusion. We also performed a dose response study using graded doses of orexin A (0, 31.25, 125 and 500 pmol) in fed and 24 h fasted rats. Orexin A 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 prior to orexin A 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.
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