Mechanism of Fatigue Studied in a Newly Developed Animal Model of Combined (Mental and Physical) Fatigue

  • Masaaki Tanaka
  • Yasuyoshi Watanabe


Recently, we established an animal model of combined (mental and physical) fatigue. To make this model, we kept rats for 5 days in a cage filled with water (23 ± 1°C) to a height of 1.5 cm, and for an evaluation of the extent of fatigue, a weight-loaded forced swimming test was used. The fatigued animals showed reduced brain energy utilization as compared with the controls. Although acutely stressed rats showed increased turnover of serotonin and dopamine in the brain, the fatigued rats did not show any change in the levels of these neurotransmitters and the metabolites in the brain regions in which the synaptic terminals are abundant. Hence, decreased energy utilization induced by prolonged deprivation of rest may introduce a vicious cycle of fatigue and lead to insufficient activation of the serotonin and dopamine systems in the brain. Since the serotonin and dopamine systems are not activated properly under the condition of fatigue, the fatigue sensation and physical activity may become insufficient, and in the terminal stage, long-term deprivation of rest may lead to death (Karoshi). We also found that by using this animal model of fatigue, we could screen for candidates for antifatigue substances for human use.


Chronic Fatigue Syndrome Dopamine System Synaptic Terminal Chronic Fatigue Syndrome Patient Central Fatigue 
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Copyright information

© Springer 2008

Authors and Affiliations

  • Masaaki Tanaka
    • 1
  • Yasuyoshi Watanabe
    • 1
  1. 1.Department of PhysiologyOsaka City University Graduate School of MedicineOsakaJapan

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