Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats
Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats
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DOI：
10.1038/sj.npp.1301028
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发表时间：
2006-12-01
影响因子：
7.6
通讯作者：
Nakaya, Yutaka
中科院分区：
文献类型：
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作者：
Morishima, Masaki;Harada, Nagakatsu;Nakaya, Yutaka
对啮齿类动物，特别是高运动活动的啮齿动物滚轮运动的神经机制的理解，将适用于促进人类运动动机的策略。海马体是几个可能调节体育锻炼的大脑区域之一。在这里，我们研究了自发性跑步-德岛四国（SPORTS）大鼠（一种新的高水平轮跑活动动物模型）的跑步活动，以及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。在运动大鼠的海马中，细胞外液中的NE水平增加，而整个组织匀浆中的NE水平即使在久坐状态下也有所下降。细胞外NE升高引起运动大鼠海马α 2-肾上腺素能受体下调。运动大鼠海马局部给予α 2-肾上腺素受体拮抗剂育亨宾，而非α 2-激动剂可乐定，可抑制高强度的跑步活动。通过降低运动大鼠海马内NE降解关键酶单胺氧化酶A （MAOA）的蛋白表达和活性水平，提高细胞外NE水平。因此，对正常Wistar大鼠氧化酶活性的抑制显著增加了轮跑活动。这些结果表明，MAOA活性的降低、胞外NE和海马α 2-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。
An understanding of neurological mechanisms for wheel running by rodents, especially with high exercise activity, would be applicable to a strategy for promotion of exercise motivation in humans. One of several brain regions that are candidates for the regulation of physical exercise is the hippocampus. Here we examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat, a new animal model for high levels of wheel-running activity, and 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 augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. Elevated extracellular NE caused downregulation of alpha 2-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of alpha 2-adrenergic receptor antagonist yohimbine, but not of alpha 2-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 to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and alpha 2-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.