Sex Differences in Activation of Forebrain Orexin Targets During Hedonic Eating

Abstract Palatable foods can stimulate appetite without hunger, and unconstrained overeating underlies obesity and binge eating disorder. Women are more prone to obesity and binge eating than men but the neural causes of individual differences are unknown. In an animal model of hedonic eating, a prior study found that females were more susceptible than males to eat palatable food when sated and that the neuropeptide orexin/hypocretisn (ORX) was crucial in both sexes. The current study examined potential forebrain targets of ORX signaling during hedonic eating. We measured Fos induction in the cortical, thalamic, striatal, and amygdalar areas that receive substantial ORX inputs and contain their receptors in hungry and sated male and female rats during consumption of a palatable (high-sucrose) food. During the test, hungry rats of both sexes ate substantial amounts, and while sated males ate much less than hungry rats, sated females ate as much as hungry rats. The Fos induction analysis identified sex differences in recruitment of specific areas of the medial prefrontal cortex (mPFC), paraventricular nucleus of the thalamus (PVT), nucleus accumbens (ACB), and central nucleus of the amygdala (CEA), and similar patterns across sexes in the insular cortex and areas of the ACB and CEA. There was a striking activation of the mPFC in sated males, who consumed the least amount food and unique correlations between the PVT and the CEA in females and the PVT and ACB in males. The study identified key functional circuits that may drive hedonic eating in a sex specific manner.