Claghorn Gerald C, Fonseca Ivana A T, Thompson Zoe, Barber Curtis, Garland Theodore
Department of Biology, University of California, Riverside, CA 92521, USA.
Department of Biology, University of California, Riverside, CA 92521, USA; Department of Physical Education, Federal University of Minas Gerais, Brazil.
Physiol Behav. 2016 Jul 1;161:145-154. doi: 10.1016/j.physbeh.2016.04.033. Epub 2016 Apr 19.
Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (P<0.0001) in a dose-dependent manner, with no dose by linetype interaction. Wheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally.
血清素（5-羟色胺；5-HT）与中枢性疲劳有关，已知5-HT1A类药物会影响啮齿动物和人类的运动耐力。我们研究了5-HT1A激动剂和拮抗剂对同一组小鼠强迫运动和自主运动的影响。这组小鼠取自4个重复品系，这些品系的小鼠经过选择性培育，与4个未选择的对照（C）品系相比，具有高水平的自主转轮运动（HR）。与C品系小鼠相比，HR品系小鼠每天在转轮上的自主运动圈数约为其3倍，并且在强迫跑步机运动中具有更强的耐力。我们假设，针对血清素受体的药物对HR和C品系小鼠的运动行为会产生不同的影响。在三项跑步机试验开始前，分别给不同组的雄性小鼠皮下注射5-HT1A拮抗剂（WAY-100,635）、5-HT1A激动剂与5-HT1A/1B部分激动剂的组合（8-OH-DPAT + 吲哚洛尔）或生理盐水。在随后三个不同夜晚的自主转轮运动期间，采用相同的处理方式。WAY-100,635降低了HR品系小鼠的跑步机耐力，但对C品系小鼠没有影响（剂量与品系类型交互作用，P = 0.0014）。8-OH-DPAT + 吲哚洛尔以剂量依赖性方式影响跑步机耐力（P < 0.0001），不存在剂量与品系类型交互作用。在8-OH-DPAT + 吲哚洛尔的最高剂量下，HR品系小鼠的转轮运动减少，但C品系小鼠未减少（剂量与品系类型，P = 0.0221），但WAY-100,635处理对其没有影响。这些结果进一步证明，血清素信号传导是强迫运动和自主运动期间运动表现的重要决定因素。虽然HR品系小鼠增加的转轮运动似乎与血清素信号传导的改变无关，但其增强的耐力能力却与之有关。更普遍地说，我们的结果表明，强迫运动和自主运动都可能受到主要作用于中枢的干预的影响。
