Mild forced exercise in young mice prevents anergia induced by dopamine depletion in late adulthood: Relation to CDNF and DARPP-32 phosphorylation patterns in nucleus accumbens

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-10-21 DOI:10.1016/j.neuropharm.2024.110197
Régulo Olivares-García , Laura López-Cruz , Carla Carratalá-Ros , Paula Matas-Navarro , John D. Salamone , Mercè Correa
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Abstract

Mesolimbic dopamine (DA) plays a critical role in behavioral activation and exertion of effort in motivated behaviors. DA antagonism and depletion in nucleus accumbens (Nacb) induces anergia in effort-based decision-making tasks. Exercise improves motor function in Parkinson's disease (PD). However, the beneficial effects of physical exercise on anergia, a symptom present in many psychiatric and neurological pathologies needs to be studied. During 9 weeks, young CD1 male mice were trained to run at a moderate speed in automatically turning running wheels (RW) (forced exercise group) or locked in static RWs (control group) in 1 h daily sessions. Both groups were tested in a 3-choice-T-maze task developed for the assessment of preference between active (RW) vs. sedentary reinforcers, and vulnerability to DA depletion-induced anergia was studied after tetrabenazine administration (TBZ; VMAT-2 blocker). Exercise did not change spontaneous preferences, did not affect body weight, plasma corticosterone levels or measures of anxiety, but it increased the cerebral DA neurotrophic factor (CDNF) in Nacb core, suggesting a neuroprotective effect in this nucleus. After TBZ administration, only the non-trained group showed a shift in relative preferences from active to sedentary options, reducing time running but increasing consumption of pellets, thus showing a typical anergic but not anhedonic effect. Moreover, only in the non-trained group, phosphorylation of DARPP-32(Thr34) increased after TBZ administration. These results are the first to show that mild forced exercise carried out from a young age to adulthood could act on Nacb-related functions, and prevent the anergia-inducing effects of DA depletion.
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年轻小鼠的轻度强迫运动可防止成年晚期多巴胺耗竭引起的兴奋:与核团中 CDNF 和 DARPP-32 磷酸化模式的关系
中叶多巴胺(DA)在动机行为的行为激活和努力中起着关键作用。多巴胺拮抗剂(DA)的拮抗作用和凹凸核(Nacb)的耗竭可诱导努力决策任务中的无动力状态。运动能改善帕金森病(PD)患者的运动功能。然而,体育锻炼对许多精神和神经疾病症状中存在的能动性的有益影响还有待研究。在为期9周的时间里,年轻的CD1雄性小鼠接受训练,以中等速度在自动转动的跑步轮(RW)中奔跑(强迫运动组)或锁定在静态RW中(对照组),每天训练1小时。这两组小鼠都接受了一项 3 选 T 迷宫任务的测试,该任务是为评估小鼠对主动强化物(RW)和静止强化物的偏好而开发的,并研究了小鼠在服用四苯嗪(TBZ;VMAT-2 阻断剂)后对 DA 耗竭诱发的兴奋的脆弱性。运动并不改变自发偏好,也不影响体重、血浆皮质酮水平或焦虑测量,但它增加了Nacb核的脑DA神经营养因子(CDNF),表明对该核有神经保护作用。给药 TBZ 后,只有未训练组的相对偏好从活动选项转向静坐选项,减少了跑步时间,但增加了颗粒食物的消耗量,从而显示出典型的能动效应,但不是失乐效应。此外,只有在非训练组中,服用 TBZ 后 DARPP-32(Thr34)的磷酸化增加。这些结果首次表明,从幼年到成年期进行的轻度强迫运动可对Nacb相关功能产生作用,并防止DA耗竭的兴奋诱导效应。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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