Univ. Bordeaux, F-33076 Bordeaux, France; CNRS, Institut de Neurosciences Cognitives et Intégratives d'Aquitaine, UMR 5287, F-33076 Bordeaux, France.
Univ. Bordeaux, F-33076 Bordeaux, France; INRA, Nutrition et Neurobiologie Intégrée, UMR 1286, F-33076 Bordeaux, France.
Neuropharmacology. 2018 Feb;129:16-25. doi: 10.1016/j.neuropharm.2017.11.021. Epub 2017 Nov 13.
Adolescence represents a critical period characterized by major neurobiological changes. Chronic stimulation of the reward system during adolescence might constitute an important factor of vulnerability to pathological development. Increasing evidences suggest that adolescent overconsumption of sweet palatable foods impact reward-based processes. However, the neurobiological bases of these deficits remain poorly understood. Previous studies have demonstrated motivational deficits for palatable foods after sweet diet exposure during adolescence that might involve the dopamine (DA) system, a central actor in incentive processes. In the present study, the impact of adolescent sugar overconsumption on the sensitivity of the DA system was tested using pharmacological (Experiment 1) and receptor expression approaches (Experiment 2). Adolescent rats received free and continuous access to 5% sucrose solution from post-natal day 30-46. At adulthood, the functionality of the DA system in motivational processes was tested using systemic injections of specific DA receptors D1R or D2R agonists and antagonists during a motivation-dependent progressive ratio task (Experiment 1). Sucrose-exposed rats showed a lower motivation for saccharin and a decreased sensitivity to the effects of both D1R and D2R stimulation and blockade. In Experiment 2, Sucrose-exposed animals presented a lower expression of both D1R and D2R in the nucleus accumbens, a central brain region for incentive processes, but not in dorsal striatum or prefrontal cortex. These findings highlight the impact of sucrose overconsumption during adolescence on DA system that may support deficits in reward-related disorders.
青春期是一个关键时期,其特点是主要的神经生物学变化。青春期期间,奖励系统的慢性刺激可能构成易患病理性发展的重要因素。越来越多的证据表明,青少年过度食用甜食会影响基于奖励的过程。然而,这些缺陷的神经生物学基础仍知之甚少。先前的研究表明,青春期暴露于甜食后,对美味食物的动机不足,这可能涉及多巴胺(DA)系统,该系统是激励过程的核心参与者。在本研究中,使用药理学方法(实验 1)和受体表达方法(实验 2)测试了青少年过度摄入糖对 DA 系统敏感性的影响。青春期大鼠从出生后第 30-46 天开始自由且持续地接触 5%蔗糖溶液。成年后,使用特定的 DA 受体 D1R 或 D2R 激动剂和拮抗剂在动机依赖性逐步比率任务中进行全身注射,测试 DA 系统在动机过程中的功能(实验 1)。蔗糖暴露的大鼠对蔗糖的动机较低,对 D1R 和 D2R 刺激和阻断的敏感性降低。在实验 2 中,蔗糖暴露的动物在伏隔核(激励过程的中枢脑区)中表现出 D1R 和 D2R 的表达水平降低,而在背侧纹状体或前额叶皮层中则没有。这些发现强调了青春期过度摄入蔗糖对 DA 系统的影响,这可能支持与奖励相关的疾病中的缺陷。