Characterization of the Effects of Fatigue on the Central Nervous System (CNS) and Drug Therapies

摘要

This study aimed to establish a rat fatigue model to test fatigue countermeasures. The model focused on central fatigue. Central fatigue associated with sleep disruption may precede peripheral fatigue, and therefore may predict impaired performance earlier than peripheral fatigue. The modified flower pot method of sleep disruption was used to induce fatigue. This study utilized hippocampal dependant tasks, the radial arm maze and the Barnes maze, to characterize the effects of sleep disruption fatigue. In addition, EEG recordings were taken to detect different sleep state changes associated with 12 hours of light phase sleep disruption. Modafinil given before sleep disruption, and at least 6 hours after the beginning of the light phase during the sleep disruption tended to improve performance in the radial arm maze. Orexin receptor antagonist SB 344867 was administered at the same time points as modafinil for a total dose of 30 mg/kg in a 12 hour sleep disruption time period. SB 344867 had an effect on Barnes maze performance. In this modified flower pot method for sleep disruption, corticosterone increased significantly during the 12 hours of sleep disruption and returned to basal levels at the end of the light phase. Elevated corticosterone leads to dendritic changes in the hippocampus, which is associated with radial arm maze and Barnes maze performance.