Orexin/hypocretin and dysregulated eating: Promotion of foraging behavior

Abstract

At its discovery, orexin/hypocretin (OX) was hypothesized to promote food intake. Subsequently, with the identification of the participation of OX in numerous other phenomena, including arousal and drug seeking, this neuropeptide was proposed to be involved in highly motivated behaviors. The present review develops the hypothesis that the primary evolutionary function of OX is to promote foraging behavior, seeking for food under conditions of limited availability. Thus, it will first describe published literature on OX and homeostatic food intake, which shows that OX neurons are activated by conditions of food deprivation and in turn stimulate food intake. Next, it will present literature on excessive and binge-like food intake, which demonstrates that OX stimulates both intake and willingness to work for palatable food. Importantly, studies show that binge-like eating can be inhibited by OX antagonists at doses far lower than those required to suppress homeostatic intake (3 mg/kg vs. 30 mg/kg), suggesting that an OX-based pharmacotherapy, at the right dose, could specifically control dysregulated eating. Finally, the review will discuss the role of OX in foraging behavior, citing literature which shows that OX neurons, which are activated during the anticipation of food reward, can promote a number of phenomena involved in successful foraging, including food-anticipatory locomotor behavior, olfactory sensitivity, visual attention, spatial memory, and mastication. Thus, OX may promote homeostatic eating, as well as binge eating of palatable food, due to its ability to stimulate and coordinate the activities involved in foraging behavior.