Centrally administered orexin A increases motivation for sweet pellets in rats

Rationale: Centrally administered orexin A induces both feeding and locomotion in rats. Thus, the feeding response following orexin A administration may be secondary to general increases in activity rather than a specific motivation to eat. Objective: The aim of the study is to determine whether orexin A increases the motivation to eat. Methods: The effect of orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol) on breakpoint was determined in male Sprague-Dawley rats with rostro-lateral hypothalamic cannulae under a progressive ratio of five schedule (PR5). The effect of orexin A (0, 31.25, 125, and 500 pmol) on pressing rate under a fixed ratio (20) schedule was obtained to analyze the time course of orexin-A-induced pressing. The effect of 24-h food deprivation on breakpoint under PR5 and the effect of orexin A (125 pmol) on free feeding (sweet pellets) and on open-field locomotor activity (0, 100, 500, and 1,000 pmol) were also tested. Results: Orexin A significantly augmented free feeding of sweet pellets, open-field locomotor activity, rate of pressing (FR20 schedule), and breakpoint (PR5 schedule), although compared to 24-h deprivation, the effect of orexin A on breakpoint was mild. However, there was a differential dose response relationship and time course of stimulation between orexin A's effects on locomotion and lever pressing. Conclusion: These data indicate that infusion of orexin A enhances free feeding by enhancing and possibly prolonging motivation to eat.