Investigating a role of orexin and 'cocaine- and amphetamine-regulated transcript' in the nucleus accumbens shell in binge eating of male rats and the relationship with impulsivity

Physiol Behav. 2022 Dec 1:257:114000. doi: 10.1016/j.physbeh.2022.114000. Epub 2022 Oct 18.

Abstract

Binge eating disorder (BED) is the most prevalent eating disorder in the adult population. It is characterized by recurrent episodes of uncontrollable overconsumption of palatable food (PF). BED is connected to several comorbidities such as obesity, major depression, and substance use disorder, and was linked to heightened levels of impulsivity. The neurobiological basis of BED is however still vaguely known. Binge eating (BE) occurs without homeostatic needs, and therefore, relates to hedonic consumption of PF. A major brain structure in the control of hedonic feeding, and part of the network regulating impulsive action, is the nucleus accumbens shell (NAcSh). The present study in rats assessed the influence of trait impulsivity on the development of BE-like feeding and the role of the orexigenic neuropeptide orexin (OX) and the anorexigenic neuropeptide cocaine- and amphetamine-regulated transcript (CART) within the NAcSh in a BE-model. The rats were initially ranked for their trait impulsivity based on a screening in the 5-choice serial reaction time task. They were subsequently introduced into a limited access-model to establish BE-like feeding with pure vegetable fat to examine a correlation between trait impulsivity and the development of BE-like feeding. The effect of bilateral infusions of the OX 1-receptor (OX1R) antagonist SB-334867 (SB) and CART-antibodies (CART-ABs) into the NAcSh was examined in relation to trait impulsivity. Further, accumbal OX1R density was evaluated by immunohistochemical staining in rats with normal and BE-like feeding behavior. We found that all animals developed stable BE-like PF intake, independent of trait impulsivity and without differences in the dynamics. The blockade of accumbal OX1Rs effectively reduced PF intake only in the control group that had daily access to PF, with impulsivity trait as a decisive factor, pointing towards alterations in orexinergic transmission in the NAcSh of rats bingeing on pure fat. This was corroborated by a lower density of OX1Rs in the NAcSh of rats with BE-like feeding behavior, precisely, in low-impulsive bingeing rats. Regardless of impulsivity trait, antagonizing CART in the NAcSh did not affect PF intake of control or bingeing animals. This suggests that endogenous accumbal CART does not influence consummatory behavior in ad libitum-fed rats with access to fat, under both normal and BE-like feeding patterns.

Keywords: Binge eating; Cocaine- and amphetamine-regulated transcript; Impulsivity; Nucleus accumbens shell; Orexin; Orexin 1-receptor.

MeSH terms

  • Amphetamines
  • Animals
  • Binge-Eating Disorder*
  • Bulimia*
  • Cocaine*
  • Eating / physiology
  • Impulsive Behavior / physiology
  • Male
  • Neuropeptides* / metabolism
  • Nucleus Accumbens / metabolism
  • Orexins
  • Rats

Substances

  • Orexins
  • Neuropeptides
  • Amphetamines
  • Cocaine