Reward deficits in an animal model of compulsive eating

Abstract

BackgroundCompulsive eating, which affects an estimated 15 million adults in the US, can be conceptualized as overeating to relieve a negative emotional state. One hypothesized underlying mechanism is diminished reward. Overeating of palatable diets alter mesolimbic dopamine neurotransmission, likely contributing to the persistence of excessive intake. However, it is not yet known if overeating of palatable food alters reward sensitivity, and whether reward is differentially altered between phases of palatable food access and withdrawal.MethodsIn this study, we investigated sensitivity to d‐Amphetamine, a dopamine releaser, in rats undergoing ad libitum palatable diet cycling, a model of compulsive eating. In this model, animals receive 2 days of access to a highly palatable, chocolate flavored, high‐sucrose diet (‘P Phase’) followed by 5 days of access to a control chow diet (‘C Phase’). In all experiments, we investigated d‐ Amphetamine sensitivity during access to the palatable diet (‘P Phase’) as well as when animals were withdrawn from palatable food (‘C Phase’). To test behavioral and molecular response to d‐ Amphetamine, we used a locomotor response assay, conditioned place preference test, intra‐cranial self‐stimulation paradigm, and in vivo microdialysis. Finally, we tested oral self‐administration of d‐Amphetamine in the home cage. To examine dopaminergic signaling targets, gene expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) were determined using quantitative polymerase chain reaction (qPCR).ResultsDuring the P phase, diet alternated rats showed reduced sensitivity to d‐Amphetamine's stimulating (locomotor assay), rewarding (CPP), and reward‐enhancing effects (ICSS). In diet cycled animals, d‐Amphetamine‐evoked dopamine efflux was blunted. Chow/Palatable rats had higher self‐administration of d‐Amphetamine during the P Phase. Levels of DAT mRNA were increased in the VTA in Chow/Palatable rats during the P Phase.ConclusionsThese results indicate that a history of overconsumption of palatable food causes reward deficits and associated alterations in the mesolimbic pathway that led to increased self‐administration of d‐ Amphetamine.Support or Funding InformationR01‐030425, F31‐DA044664This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.