Effects of oleoylethanolamide on mesolimbic dopaminergic transmission in an animal model of binge eating

Binge eating episodes are characterized by uncontrollable, distressing eating of a large amount of highly palatable food (HPF). These episodes represent a central feature of binge eating disorder (BED), in which one of the mechanisms underlying the pathophysiology in the central nervous system is represented by the disruption of the dopamine (DA) rewarding circuitry. The endogenous satiety signal Oleoylethanolamide (OEA) has recently emerged as a potential novel pharmacological target for controlling eating disorders. In the present study we aim to investigate the effect of OEA on HPF intake and on the modulation of DA release in the nucleus accumbens (NAcc) in a model of BED. We used a BED model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress). OEA was administered (10 mg/kg intraperitoneally) to two different sets of BED and control rats. In the first set, rats were subjected to a microdialysis experiment performed within the shell of the NAcc (AcbSh) and feeding behavior and DA extracellular levels were analyzed. In the second set of rats, 2 hours after OEA administration rats were sacrificed, the brains were collected and then microdissected with the cryostat. Monoamines were extracted from brain sections containing NAcc and both extracellular and tissue DA levels were analyzed by using HPLC. Our results revealed that OEA: exerts its anorexigenic effect in our BED model by significantly reducing the HPF intake; restores “normal” feeding behavior by preventing DA efflux in the AcbSh during frustration stress procedure; decreases both intracellular and extracellular DA levels in the NAcc of BED animals. Overall these results support the hypothesis that OEA might represent a novel potential pharma-cological target for the treatment of aberrant eating models such as BED. This work was supported by a grant (PRIN 2012JTX3KL_002) of the Italian Ministry of Education, University and Research. The authors declare no actual or potential conflicts of interest