Laboratori de Neurofarmacologia. Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Cellular & Systems Neurobiology, Systems Biology Program, The Barcelona Institute of Science and Technology, Centre for Genomic Regulation (CRG), Barcelona, Spain.
Addict Biol. 2018 Mar;23(2):544-555. doi: 10.1111/adb.12597. Epub 2017 Dec 28.
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.
治疗肥胖的一个主要问题是，在维持能量平衡饮食后，恢复异常进食习惯的比率很高。进食行为的改变，如强迫样行为和对食物摄入缺乏自我控制，在复胖中起着关键作用。在这项研究中，我们使用了一种食物寻求行为的操作性范式，针对两种不同的饮食诱导肥胖模型，即自由选择巧克力混合物饮食和高脂肪饮食，这两种模型都具有快速发展肥胖或社会上经常摄入的不健康食物的有效性。在这两种肥胖小鼠模型中，对美味巧克力丸的享乐价值的操作性表现和动机都有所降低。然而，只有暴露于高脂肪饮食的小鼠在没有强化物的情况下表现出强迫样行为增加，进一步表现为操作性学习受损、冲动性增强和灵活性降低。我们使用主成分分析来全面识别导致饮食组之间差异的特定行为。学习障碍和不灵活的行为导致了第一个主成分，解释了高脂肪饮食小鼠表型中最大比例的方差。强化、冲动和强迫是解释巧克力混合物小鼠行为表型差异的第二个主成分的主要贡献者。这些行为并不是巧克力组所独有的，因为一些高脂肪个体在这个成分上也表现出相似的值。这些数据表明，长期摄入高热量饮食会使操作性行为学习、行为灵活性、冲动样和强迫样行为发生不同程度的改变，这些影响取决于每种特定饮食的暴露。
