1. ¹Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima City, Japan
2. ²Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima City, Japan

Correspondence: Dr N Harada, Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan. Tel: +81 88 633 7090; Fax: +81 88 633 7113; E-mail: harada@nutr.med.tokushima-u.ac.jp

Received 25 August 2005; Revised 6 December 2005; Accepted 8 December 2005; Published online 18 January 2006.

Abstract

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 ₂-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of ₂-adrenergic receptor antagonist yohimbine, but not of 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 ₂-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.