Ozone-induced paradoxical sleep decrease is related to diminished acetylcholine levels in the medial preoptic area in rats.
Ozone (O3) produces significant effects on sleep, characterized specially by a decrease in paradoxical sleep (PS) and increase in slow-wave sleep (SWS), which in turn represent a sleep-wake cycle disruption. On the other hand, neuronal activity recorded in the cholinoceptive hypothalamic medial preoptic area (MPO) has been involved in the regulation of sleep. However, there is no direct evidence on the role that acetylcholine (Ach) release in the MPO plays in the sleep-wake cycle. In order to study this relation, we measured the Ach concentration in dialysates collected from MPO in rats exposed to coal-filtered air (clean air) for 48 h and in rats exposed to clean air for 24 h followed by 24-h of O3 exposure to 0.5 ppm. Polygraphic sleep records were taken simultaneously to neurochemical sampling. O3 was employed to disrupt the sleep-wake cycle and relate these changes with concomitant disruptions in Ach concentration dialyzed from MPO. A clear circadian pattern of Ach concentration was observed in dialysates from MPO and also in PS, SWS and wakefulness of rats exposed to filtered air. However, O3 exposure decreased the PS by 65% (Mann-Whitney's U-test, p<or=0.0003) and a concomitant decrease of extracellular Ach of 58% (p<or=0.0239) was observed during the light phase. These changes were maintained during the dark phase, although it was also observed that slow-wave sleep increased by 75% (p<or=0.0013) while wakefulness was decreased in 35% (p<or=0.0007). We conclude that Ach release in MPO follows a circadian rhythm that is disrupted by O3 exposure, and these changes are strongly associated with the O3-induced PS disruptions.