A major problem in treating obesity is the high rate of relapse to abnormal food-taking habits after maintaining an energy balanced diet. Alterations of eating behavior such as compulsive-like behavior and lack of self-control over food intake play a critical role in relapse. In this study, we used an operant paradigm of food-seeking behavior on two different diet-induced obesity models, a free-choice chocolate-mixture diet and a high-fat diet with face validity for a rapid development of obesity or for unhealthy food regularly consumed in our societies. A reduced operant performance and motivation for the hedonic value of palatable chocolate pellets was revealed in both obesity mouse models. However, only mice exposed to high-fat diet showed an increased compulsive-like behavior in the absence of the reinforcer further characterized by impaired operant learning, enhanced impulsivity and intensified inflexibility. We used principal component analysis to globally identify the specific behaviors responsible for the differences among diet groups. Learning impairment and inflexible behaviors contributed to a first principal component, explaining the largest proportion of the variance in the high-fat diet mice phenotype. Reinforcement, impulsion and compulsion were the main contributors to the second principal component explaining the differences in the chocolate-mixture mice behavioral phenotype. These behaviors were not exclusive of chocolate group because some high-fat individuals showed similar values on this component. These data indicate that extended access to hypercaloric diets differentially modifies operant behavior learning, behavioral flexibility, impulsive-like and compulsive-like behavior, and these effects were dependent on the exposure to each specific diet.

This work was supported by the DG Research of the European Commission FP7 (#HEALTH-F2 2013-602891 and PHECOMP #LHSM-CT-2007-037669), the Spanish ‘RETICS-Instituto de Salud Carlos III’ (#RD16/0017/0020), the Spanish ‘Ministerio de Economia y Competitividad’ (#SAF-2014-59648P), the ‘Plan nacional sobre drogas’ (#PNSD-2013-5068), the Catalan Government ‘AGAUR-Generalitat de Catalunya’ (#2014-SGR-1547) and the Catalan foundation ‘La Marató de TV3’ (#2016/20-30). The laboratory of M.D. is supported by DIUE de la Generalitat de Catalunya (Grups consolidats SGR 2014/1125). This work was supported by Fondation Jérôme Lejeune (Paris, France), MINECO (SAF2013-49129-C2-1-R), CDTI (‘Smartfoods’) and EU (Era Net Neuron PCIN-2013-060). The CRG is a Center of Excellence Severo Ochoa SEV-2012-0208. The CIBER of Rare Diseases is an initiative of the ISCIII. The laboratory of C.N. acknowledges the funding from the Spanish Ministry of Economy and Finance (MINECO), grant number BFU2011-28575. J.E. receivedthe FI grant from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) de la Generalitat de Catalunya