Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.
Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.
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内源性大麻素的循环水平对自愿运动反应强烈，在选择性饲养的高自愿轮跑小鼠中发生改变，并且在性别之间存在差异。
DOI：
10.1016/j.physbeh.2016.11.041
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发表时间：
2017
影响因子：
2.9
通讯作者：
DiPatrizio,Nicholas
中科院分区：
文献类型：
--
作者：
Thompson,Zoe;Argueta,Donovan;GarlandJr,Theodore;DiPatrizio,Nicholas
内源性大麻素系统具有许多生理作用，包括调节能量平衡、食物奖励和自主运动。 1 型大麻素受体的信号传导与啮齿动物在轮子上进行自愿运动的动机特别相关。我们研究了四个复制品系的高跑者 (HR) 小鼠，这些小鼠根据六天轮子使用周期中第五天和第六天的平均轮转数选择性繁殖了 81 代。培育四个额外的复制系，不考虑轮式运行，并作为可能导致系间分歧的随机遗传效应的对照（C）。平均而言，HR 系小鼠每天自愿在轮子上跑步的次数是 C 系小鼠的三倍。我们测试了一般假设，即 HR 和 C 小鼠之间内源性大麻素（即 2-花生四烯酰甘油 [2-AG] 和 anandamide [AEA]）的循环水平存在性别特异性差异。 50 只雄性和 50 只雌性小鼠被允许使用轮子六天，而另外 50 只雄性和 50 只雌性小鼠则被禁止使用轮子（所有组的一半为 HR，一半为 C）。在车轮进入或没有车轮进入的第六个晚上的高峰跑步时间通过心脏穿刺收集血液，然后通过超高效液相色谱结合串联质谱分析 2-AG 和 AEA 含量。我们观察到性别、线型和车轮接触对 2-AG 浓度的显着三向相互作用，女性的水平通常低于男性，并且车轮接触降低了一些亚组（但不是所有亚组）的 2-AG 水平。采样前几分钟或几小时内的轮转数并不能定量预测组内血浆 2-AG 水平。我们还观察到 AEA 水平的线型与轮接触相互作用的趋势，轮接触降低了 HR 小鼠中 AEA 的血浆浓度，而提高了 C 小鼠中的 AEA 血浆浓度。此外，女性的 AEA 浓度往往高于男性。对于带轮子的小鼠，采样前 30 分钟内的跑步量是组内血浆 AEA 的显着正向预测因子，HR 小鼠的 AEA 水平显着低于 C 小鼠。我们的结果表明，自愿运动改变了内源性大麻素的循环水平，并进一步证明了自愿运动的选择性育种与内源性大麻素系统的进化变化有关。
The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion. Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels. We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access. Four additional replicate lines are bred without regard to wheel running, and serve as controls (C) for random genetic effects that may cause divergence among lines. On average, mice from HR lines voluntarily run on wheels three times more than C mice on a daily basis. We tested the general hypothesis that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG] and anandamide [AEA]) differ between HR and C mice in a sex-specific manner. Fifty male and 50 female mice were allowed access to wheels for six days, while another 50 males and 50 females were kept without access to wheels (half HR, half C for all groups). Blood was collected by cardiac puncture during the time of peak running on the sixth night of wheel access or no wheel access, and later analyzed for 2-AG and AEA content by ultra-performance liquid chromatography coupled to tandem mass spectrometry. We observed a significant three-way interaction among sex, linetype, and wheel access for 2-AG concentrations, with females generally having lower levels than males and wheel access lowering 2-AG levels in some but not all subgroups. The number of wheel revolutions in the minutes or hours immediately prior to sampling did not quantitatively predict plasma 2-AG levels within groups. We also observed a trend for a linetype-by-wheel access interaction for AEA levels, with wheel access lowering plasma concentrations of AEA in HR mice, while raising them in C mice. In addition, females tended to have higher AEA concentrations than males. For mice housed with wheels, the amount of running during the 30 min before sampling was a significant positive predictor of plasma AEA within groups, and HR mice had significantly lower levels of AEA than C mice. Our results suggest that voluntary exercise alters circulating levels of endocannabinoids, and further demonstrate that selective breeding for voluntary exercise is associated with evolutionary changes in the endocannabinoid system.