Velázquez-Sánchez Clara, Ferragud Antonio, Moore Catherine F, Everitt Barry J, Sabino Valentina, Cottone Pietro
Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Behavioral and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK.
Neuropsychopharmacology. 2014 Sep;39(10):2463-72. doi: 10.1038/npp.2014.98. Epub 2014 Apr 29.
Impulsivity is a behavioral trait frequently seen not only in drug-addicted individuals but also in individuals who pathologically overeat. However, whether impulsivity predates the development of uncontrollable feeding is unknown. In this study, we hypothesized that a high impulsivity trait precedes and confers vulnerability for food addiction-like behavior. For this purpose, we trained ad libitum-fed male Wistar rats in a differential reinforcement of low rates of responding (DRL) task to select Low- and High-impulsive rats. Then, we allowed Low- and High-impulsive rats to self-administer a highly palatable diet (Palatable group) or a regular chow diet (Chow group) in 1-h daily sessions, under fixed ratio (FR) 1, FR3, FR5, and under a progressive ratio (PR) schedules of reinforcement. In addition, we tested the compulsiveness for food in Low- and High-impulsive rats by measuring the food eaten in the aversive, open compartment of a light/dark conflict test. Finally, we measured the expression of the transcription factor ΔFosB in the shell and the core of the nucleus accumbens, which is a marker for neuroadaptive changes following addictive drug exposure. The data we obtained demonstrate that impulsivity is a trait that predicts the development of food addiction-like behaviors, including: (i) excessive intake, (ii) heightened motivation for food, and (iii) compulsive-like eating, when rats are given access to highly palatable food. In addition, we show that the food addiction phenotype in high impulsive subjects is characterized by an increased expression of the transcription factor ΔFosB in the nucleus accumbens shell. These results reveal that impulsivity confers an increased propensity to develop uncontrollable overeating of palatable food.
冲动性是一种常见的行为特征,不仅在吸毒成瘾者中可见,在病理性暴饮暴食者中也很常见。然而,冲动性是否先于无法控制的进食行为出现尚不清楚。在本研究中,我们假设高冲动性特质先于食物成瘾样行为的发展并使其易感性增加。为此,我们在低反应率差异强化(DRL)任务中对自由进食的雄性Wistar大鼠进行训练,以挑选出低冲动性和高冲动性大鼠。然后,我们让低冲动性和高冲动性大鼠在每天1小时的实验时段内,按照固定比率(FR)1、FR3、FR5以及累进比率(PR)强化程序,自行摄取美味食物(美味组)或普通食物(普通组)。此外,我们通过测量明暗冲突试验中厌恶的开放隔间内大鼠的进食量,来测试低冲动性和高冲动性大鼠对食物的强迫性。最后,我们测量了伏隔核壳部和核心中转录因子ΔFosB的表达,它是成瘾性药物暴露后神经适应性变化的标志物。我们获得的数据表明,冲动性是一种能够预测食物成瘾样行为发展的特质,包括:(i)过度摄入,(ii)对食物的动机增强,以及(iii)强迫性进食,当大鼠能够获取高度美味的食物时。此外,我们还表明,高冲动性受试者的食物成瘾表型特征是伏隔核壳部转录因子ΔFosB的表达增加。这些结果揭示,冲动性会增加发展为对美味食物无法控制的暴饮暴食的倾向。