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Dopaminergic Modulation of Forced Running Performance in Adolescent Rats: Role of Striatal D1 and Extra-striatal D2 Dopamine Receptors
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2021-01-04 , DOI: 10.1007/s12035-020-02252-2
Angel Toval 1, 2 , Daniel Garrigos 1, 2 , Yevheniy Kutsenko 1, 2 , Miroljub Popović 1, 2 , Bruno Ribeiro Do-Couto 3 , Nicanor Morales-Delgado 1, 2, 4 , Kuei Y Tseng 5 , José Luis Ferran 1, 2
Affiliation  

Improving exercise capacity during adolescence impacts positively on cognitive and motor functions. However, the neural mechanisms contributing to enhance physical performance during this sensitive period remain poorly understood. Such knowledge could help to optimize exercise programs and promote a healthy physical and cognitive development in youth athletes. The central dopamine system is of great interest because of its role in regulating motor behavior through the activation of D1 and D2 receptors. Thus, the aim of the present study is to determine whether D1 or D2 receptor signaling contributes to modulate the exercise capacity during adolescence and if this modulation takes place through the striatum. To test this, we used a rodent model of forced running wheel that we implemented recently to assess the exercise capacity. Briefly, rats were exposed to an 8-day period of habituation in the running wheel before assessing their locomotor performance in response to an incremental exercise test, in which the speed was gradually increased until exhaustion. We found that systemic administration of D1-like (SCH23390) and/or D2-like (raclopride) receptor antagonists prior to the incremental test reduced the duration of forced running in a dose-dependent manner. Similarly, locomotor activity in the open field was decreased by the dopamine antagonists. Interestingly, this was not the case following intrastriatal infusion of an effective dose of SCH23390, which decreased motor performance during the incremental test without disrupting the behavioral response in the open field. Surprisingly, intrastriatal delivery of raclopride failed to impact the duration of forced running. Altogether, these results indicate that the level of locomotor response to incremental loads of forced running in adolescent rats is dopamine dependent and mechanistically linked to the activation of striatal D1 and extra-striatal D2 receptors.



中文翻译:


青春期大鼠强迫跑步表现的多巴胺能调节:纹状体 D1 和纹状体外 D2 多巴胺受体的作用



提高青春期的运动能力对认知和运动功能产生积极影响。然而,在这个敏感时期有助于增强身体表现的神经机制仍然知之甚少。这些知识可以帮助优化锻炼计划并促进青少年运动员健康的身体和认知发展。中枢多巴胺系统因其通过激活 D1 和 D2 受体来调节运动行为的作用而引起人们极大的兴趣。因此,本研究的目的是确定 D1 或 D2 受体信号传导是否有助于调节青春期的运动能力,以及这种调节是否通过纹状体发生。为了测试这一点,我们使用了最近实施的强制跑轮啮齿动物模型来评估运动能力。简而言之,大鼠在跑轮上进行为期 8 天的习惯期,然后评估其响应增量运动测试的运动性能,其中速度逐渐增加直至筋疲力尽。我们发现,在增量测试之前全身施用 D1 样(SCH23390)和/或 D2 样(雷氯必利)受体拮抗剂以剂量依赖性方式减少强迫跑步的持续时间。类似地,多巴胺拮抗剂降低了旷场的运动活性。有趣的是,在纹状体内输注有效剂量的 SCH23390 后情况并非如此,它在增量测试期间降低了运动表现,但没有破坏开放视野中的行为反应。令人惊讶的是,纹状体内注射雷氯必利并没有影响强迫跑步的持续时间。 总而言之,这些结果表明,青春期大鼠对强迫跑步增量负荷的运动反应水平是多巴胺依赖性的,并且在机制上与纹状体 D1 和纹状体外 D2 受体的激活有关。

更新日期:2021-01-04
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