Central effects of the satiety signal oleoylethanolamide in an animal model of frustration stress-induced binge eating disorder

Binge-eating disorder (BED), characterized by compulsive and uncontrollable overeating of highly palatable food (HPF), has been associated to altered dopamine (DA) and serotonin (5-HT) brain signalling. The satiety signal oleoylethanolamide (OEA) has emerged as a potential novel pharmacological tool for controlling aberrant eating patterns, by restoring a normal brain dopaminergic response, when it is deregulated by an excessive dietary fat intake. Based on these premises in this study we investigated in a rat model of BED the effects of OEA: 1) on Fos expression and tissue monoamine (DA, 5-HT, Noradrenaline) concentrations in brain areas controlling feeding and reward; 2) on the modulation of DA release within the shell of the nucleus accumbens (AcbSh). In our model, female rats with a history of intermittent food restriction and HPF consumption showed binge-like food intake after the exposure to a “frustration stress” consisting of the sight of unreachable HPF (BED rats). Control rats were exposed to the same experimental manipulations except for food restriction and did not show any binge eating behaviour. OEA was administered (10 mg/kg i.p.) to two different sets of both BED and control rats. A first set was sacrificed 2 hours after OEA administration; their brains were partly sliced into 20 μm coronal sections (immunostained for Fos), and partly microdissected for monoamine determination by HPLC.The second set of rats was subjected to in vivo microdialysis of the AcbSh, collecting dialysates every 15 min, and was first intraperitoneally treated with OEA (10 mg/kg) and then challenged with a subcutaneous dose of amphetamine (0.5 mg/kg). DA dialysate levels were analysed by HPLC. OEA administration was able to restore a “normal” brain activity, by reducing the stress-induced Fos increase in brain areas regulating feeding and the dopaminergic signalling. Moreover, we found that OEA treatment decreased DA efflux in the AcbSh, following either stress exposure or amphetamine challenge. At tissue level, we found that OEA also reduced DA concentration within the Acb of BED rats. As far as the serotonergic system, we found that OEA is able to enhance 5-HT transmission in most of the brain areas analysed, selectively in bingeing rats. Overall, these results further enrich our current knowledge on the central effects of OEA and support, for the first time, the hypothesis that OEA might represent a novel potential pharmacological target for the treatment of BED.