CALL FOR PAPERS Physiological Regulation of Appetite Orexin A-induced feeding is augmented by caloric challenge

Thorpe, A. J., J. A. Teske, and C. M. Kotz. Orexin A-induced feeding is augmented by caloric challenge. Am J Physiol Regul Integr Comp Physiol 289: R367–R372, 2005; doi:10.1152/ajpregu.00737.2004.— 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 dosedependently 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 doseresponse 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.