Monoamine dynamics in control of spontaneous physical activity in rats

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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.