Multiple subtypes of opioid receptors regulate binge‐like (BE) feeding in rodents on an intermittent access schedule

Abstract

Binge eating disorder (BED) affects approximately 3% of adults in the USA and is characterized by repeated episodes of eating unusually large amounts of food in a short period of time without engaging in compensatory behaviors. Interestingly, a significant comorbidity with substance abuse exists in patients with BED. Opioid peptides are known to regulate appetitive behavior. Moreover, opioid receptor antagonists (OpRA) are used clinically in the treatment of alcohol and substance abuse. In both rats and mice, the pan OpRA LY255582 was effective in reducing BE at doses that did not affect control 24 hour intake. In rats, similar reductions in BE were observed using the mu and delta selective OpRAs LY2491481 and naltriben, respectively. The kappa selective OpRA LY2444296 was ineffective in reducing BE in rats. In order to confirm our pharmacology findings using genetic models, we evaluated BE in OpR knockout mice using a similar intermittent access paradigm. Unlike our antagonist studies, no differences in BE were observed in either the mu or delta receptor mutants compared to wildtypes. Interestingly, spontaneous free access feeding and BE were increased in the kappa receptor specific and mu‐delta‐kappa combinatorial mutants in comparison to wildtypes. Our data support that endogenous opioids modulate BE in a complex manner in rodents.