Foley Teresa E, Greenwood Benjamin N, Day Heidi E W, Koch Lauren G, Britton Steven L, Fleshner Monika
Department of Integrative Physiology, University of Colorado, Boulder, CO 80309 0354, USA.
Behav Brain Res. 2006 Nov 1;174(1):132-42. doi: 10.1016/j.bbr.2006.07.018. Epub 2006 Aug 28.
Although alteration to peripheral systems at the skeletal muscle level can contribute to one's ability to sustain endurance capacity, neural circuits regulating fatigue may also play a critical role. Previous studies demonstrated that increasing brain serotonin (5-HT) release is sufficient to hasten the onset of exercise-induced fatigue, while manipulations that increase brain dopamine (DA) release can delay the onset of fatigue. These results suggest that individual differences in endurance capacity could be due to factors capable of influencing the activity of 5-HT and DA systems. We evaluated possible differences in central fatigue pathways between two contrasting rat groups selectively bred for high (HCR) or low (LCR) capacity running. Using quantitative in situ hybridization, we measured messenger RNA (mRNA) levels of tryptophan hydroxylase (TPH), 5-HT transporter (5-HTT), 5-HT1A and 5-HT1B autoreceptors, dopamine receptor-D2 (DR-D2) autoreceptors and postsynaptic receptors, and dopamine receptor-D1 (DR-D1) postsynaptic receptors, in discrete brain regions of HCR and LCR. HCR expressed higher levels of 5-HT1B autoreceptor mRNA in the raphe nuclei relative to LCR, but similar levels of TPH, 5-HTT, and 5-HT1A mRNA in these areas. Surprisingly, HCR expressed higher levels of DR-D2 autoreceptor mRNA in the midbrain, while simultaneously expressing greater DR-D2 postsynaptic mRNA in the striatum compared to LCR. There were no differences in DR-D1 mRNA levels in the striatum or cortex between groups. These data suggest that central serotonergic and dopaminergic systems may be involved in the mechanisms by which HCR have delayed onset of exercise-induced fatigue compared to LCR.
虽然骨骼肌水平的外周系统改变有助于一个人维持耐力的能力，但调节疲劳的神经回路可能也起着关键作用。先前的研究表明，增加大脑中血清素（5-羟色胺，5-HT）的释放足以加速运动诱导疲劳的发作，而增加大脑多巴胺（DA）释放的操作则可以延迟疲劳的发作。这些结果表明，耐力能力的个体差异可能归因于能够影响5-HT和DA系统活性的因素。我们评估了两组选择性培育的具有高（HCR）或低（LCR）跑步能力的对比大鼠之间中枢疲劳通路的可能差异。使用定量原位杂交技术，我们测量了HCR和LCR大鼠离散脑区中色氨酸羟化酶（TPH）、5-HT转运体（5-HTT）、5-HT1A和5-HT1B自身受体、多巴胺受体-D2（DR-D2）自身受体和突触后受体以及多巴胺受体-D1（DR-D1）突触后受体的信使核糖核酸（mRNA）水平。相对于LCR，HCR在中缝核中表达更高水平的5-HT1B自身受体mRNA，但在这些区域中TPH、5-HTT和5-HT1A mRNA水平相似。令人惊讶的是，与LCR相比，HCR在中脑表达更高水平的DR-D2自身受体mRNA，同时在纹状体中表达更高水平的DR-D2突触后mRNA。两组之间纹状体或皮质中DR-D1 mRNA水平没有差异。这些数据表明，中枢5-羟色胺能和多巴胺能系统可能参与了HCR与LCR相比运动诱导疲劳发作延迟的机制。
