Monoamine dynamics in control of spontaneous physical activity in rats

我们创造了一个原始的Wistar系列大鼠，显示出更高水平的轮式跑步，运动（自发跑步-德岛四国）。雄性运动大鼠自愿在跑步轮中跑步的时间几乎是雄性对照组Wistar大鼠的6倍。我们研究了运动大鼠的跑步活动，以阐明啮齿动物轮式跑步的神经机制，特别是它与海马去甲肾上腺素（NE）系统的关系，包括NE、肾上腺素能受体和单胺降解酶的水平。运动大鼠海马细胞外液NE水平升高，全组织匀浆NE水平降低。运动大鼠海马局部给药a2-肾上腺素能受体拮抗剂育亨宾，而不给药a2-受体激动剂可乐定，可抑制高跑活性。运动大鼠海马单胺氧化酶A （monoamine oxidase A， MAOA）蛋白表达和活性水平降低，导致胞外NE水平升高。MAOA是NE降解的关键酶。因此，抑制正常Wistar大鼠的MAOA活性可显著增加轮跑活动。这些结果表明，MAOA活性的降低、胞外NE和海马a2-肾上腺素能受体的升高决定了运动大鼠运动行为心理调节的神经基础。我们还发现，运动大鼠经常与左心房血栓相关，可能是由于凝血能力增强、粘附分子表达增加以及高血压引起的内皮损伤。因此，该大鼠也可作为高血压心房血栓形成的模型。

We generated an original Wistar line of rats that displayed increased levels of wheel running, SPORTS (Spontaneously-Running-Tokushima-Shikoku). Male SPORTS rats ran voluntarily in a running wheel almost six times longer than male control Wistar rats. We examined the running activity of SPORTS rat, to clarify neurological mechanisms for wheel running by rodents, especially its relation with the hippocampal norepinephrine (NE) system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was elavated, whereas the level in the homogenate of the whole tissue was decreased. Local administration of a2-adrenergic receptor antagonist yohimbine, but not of a2-agonist clonidine, into the hippocampus suppressed high running activity in SPORTS rats. The protein expression and the activity levels of monoamine oxidase A (MAOA), a critical enzyme for the degradation of NE, were decreased in the hippocampus of SPORTS rats, which in turn increased extracellular NE level. Thus, inhibition of MAOA activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and a2-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.We also found that SPORTS rats frequently are associated with left atrial thrombi, presumably due to increased coagulability, increased expression of adhesion molecules, and endothelial damage due to hypertension. Thus, this rats also serve as a model of atrial thrombosis in hypertension.