Modafinil is a newly discovered waking substance now being used in the treatment of
hypersomnia and
narcolepsy. We have shown previously in the cat that, unlike
amphetamine,
modafinil induces long-lasting wakefulness (W) without behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous
catecholamines. To further characterize the awakening properties of
modafinil and current psychostimulants in experimental models of
hypersomnia, we examined the effect of
oral administration of placebo,
modafinil (5 mg kg-1) or
amphetamine (1 mg kg-1) on the sleep/wake cycle and power spectral density (PSD) in cats after an 18-h water-tank
sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both
modafinil and
amphetamine induced suppression of cortical slow activity and a waking state lasting 6-8 h. After the
amphetamine-induced waking period, both deep slow wave sleep (SWS2) and paradoxical sleep (PS) occurred in greater amounts than after placebo and the PSD during SWS was also increased. Thus, the cumulative time spent in W during a 48-h period was similar to that with placebo, indicating enhanced sleep rebound. In contrast, after the
modafinil-induced W, the occurrence and evolution of SWS2 or PS, as well as the PSD during SWS, were similar to those seen with placebo during the same period, so that the total time spent in W in a 48-h period remained significantly higher than the control level, indicating no additional sleep rebound. These results indicate that
modafinil is effective against
somnolence and
hypersomnia and does not produce a subsequent increase in sleep and suggest that the pharmacological profile of
modafinil is different from that of
amphetamine.