Intermittent, extended access to preferred food leads to escalated food reinforcement and cyclic whole-body metabolism in rats: Sex differences and individual vulnerability.

Compulsive binge eating is a hallmark of binge eating disorder and bulimia nervosa and is implicated in some obesity cases. Eating disorders are sexually dimorphic, with females more often affected than males. Animal models of binge-like eating based on intermittent access to palatable food exist; but, little is known regarding sex differences or individual vulnerability in these models with respect to the reinforcing efficacy of food, the development of compulsive- and binge-like eating, or associated changes in whole-body metabolism or body composition. Adolescent male (n = 24) and female (n = 32) Wistar rats were maintained on chow or a preferred, high-sucrose, chocolate-flavored diet in continuous or intermittent, extended access conditions. Body weight and composition, intake, fixed- and progressive-ratio operant self-administration, and whole body energy expenditure and respiratory exchange ratios were measured across an 11-week study period. Subgroup analyses were conducted to differentiate compulsive-like "high responder" intermittent access rats that escalated to extreme progressive-ratio self-administration performance vs. more resistant "low responders." Female rats had greater reinforcing efficacy of food than males in all diet conditions and were more often classified as "high responders". In both sexes, rats with intermittent access showed cycling of fuel substrate utilization and whole-body energy expenditure. Further, "high-responding" intermittent access female rats had especially elevated respiratory exchange ratios, indicating a fat-sparing phenotype. Future studies are needed to better understand the molecular and neurobiological basis of the sex and individual differences we have observed in rats and their translational impact for humans with compulsive, binge eating disorders.