Fasting influences conditioned memory for food preference through the orexin system: Hypothesis gained from studies in the rat

Abstract

A large variety of behaviors that are essential for animal survival depend on the processing and perception of surrounding smells present in the natural environment. In particular, food-search behavior, which is conditioned by hunger, is directly driven by the perception of odors associated with food, and feeding status modulates olfactory sensitivity. The orexigenic hypothalamic peptide orexin A, one of the main central and peripheral hormones that triggers food intake, has been shown to increase olfactory sensitivity in various experimental conditions including the conditioned odor aversion learning paradigm. Conditioned odor aversion is an associative task that corresponds to the association between an olfactory conditioned stimulus and a delayed gastric malaise. Previous studies have shown that this association is formed only if the delay separating the conditioned stimulus presentation from the malaise is short, suggesting that the memory trace of the odor is relatively unstable. To test the selective impact of the orexin system in olfactory sensitivity, a recent study compared the effects of fasting and of central infusion of orexin A during the acquisition of conditioned odor aversion. Results showed that the increased olfactory sensitivity induced by fasting or by orexin infusion was accompanied by enhanced conditioned odor aversion learning performances. In reference to the duration of action of orexin, the present work details the results obtained during the successive conditioned odor aversion extinction tests and suggests a hypothesis concerning the role of the orexin component of fasting on the memory processes underlying the odormalaise association during conditioned odor aversion. Moreover, referring to previous data in the literature, we suggest a functional circuit model where fasting modulates olfactory memory processes through direct and/or indirect activation of particular orexin brain targets including the olfactory bulb, the locus coeruleus, and the amygdala.