Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder

Abstract

Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg−1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior.

The Melanocortin System behind the Dysfunctional Eating Behaviors

“…The result of this study suggests a sex-dependent responsivity in the basal HPA axis tone and acute stress-induced corticosterone in rodents with MC4R mutation [ 202 ]. Considering the heightened stress reactivity found in female rats with deficient MC4R activity [ 202 ], and that stress has been associated with EE [ 37 , 38 ] and binge eating behavior [ 38 , 204 , 205 , 206 ], it would be interesting in the future to evaluate the potential involvement of MC4R signaling in a female rat model of binge eating, in which the binge eating episode is elicited by a combination of food restriction plus stress [ 86 , 87 ] and by using HPF, in order to promote the aberrant feeding behavior and to increase the motivation to overconsume food [ 38 , 87 , 207 , 208 , 209 ].…”

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

“…The majority of OEA’s biological functions explains its potential interest as a pharmacological target for the treatment of obesity and eating-related disorders [ 1 , 15 , 16 ]. Therefore, as a drug, OEA reduces food intake and body weight gain [ 3 , 17 , 18 ] in both lean and obese rodents.…”

Serum metabolic signature of binge‐like palatable food consumption in female rats by nuclear magnetic resonance spectroscopy

“…Thirty-two female 52-day-old Sprague-Dawley rats (Charles River, Italy) were submitted to the binge-eating protocol as described in previous works 25,[47][48][49] and in the supporting information.…”