Indomethacin reverts sleep disorders produced by ozone exposure in rats

Ozone (O(3)) exposure causes pulmonary biochemical changes both in humans and experimental animals, inducing the release of inflammatory mediators such as cytokines and eicosanoids. Some of these reaction products have been characterized as endogenous sleep-promoting substances and have been implicated in the development of sleepiness in patients with inflammatory disease. Furthermore, sleep alterations are known to occur in O(3)-exposed humans and experimental animals. In order to test the probable involvement of such inflammatory mediators in O(3)-induced sleep disorders, we blocked prostaglandin synthesis administrating the cyclooxygenase inhibitor indomethacin (IM) and compared conventional electrographic sleep parameters in rats under four different experimental conditions: treatment with IM alone, O(3)-exposure, pre-treatment with IM plus O(3) exposure, and control conditions. We found that O(3) exposure increased slow wave sleep (SWS) and decreased rapid eye movement sleep (REMs) significantly, while IM pre-treatment reduced these O(3)-induced sleep disorders. IM treatment alone did not affect sleep. These findings strongly support a role for inflammatory mediators in O(3) exposure-induced neurological alterations.