Abstract
Two experimental animal models for central fatigue have been developed by excessive activation of the central nervous system of rats; induction of cortical spreading depression, the propagation of neuronal membrane depolarization throughout the cerebral cortex, and long-term intracranial self-stimulation. We have reported that prostaglandins including PGD2, PGE2, and PGF2α were produced by COX-2 expression in neurons in the cerebral cortex following cortical spreading depression. In such a model for neuronal excitation in the cortex, the amount of non-REM sleep, but not of REM sleep, increased subsequently for several hours in the animals, and the increase was completely attenuated by application of NS-398, a COX-2 inhibitor. In a long-term intracranial self-stimulation study, resting behavior and non-REM sleep appeared a few hours after the start of stimulation, and such behavioral changes were also inhibited by application of an inhibitor of COX-2. These observations indicate that arachidonic acid cascade plays an important role in a common molecular and neural system in such animal models for fatigue following neuronal activation in the central nervous system, and relieves excessive brain activity by inducing resting behavior and non-REM sleep. [J Physiol Sci. 2008;58 Suppl:S18]
