Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat

Modafinil is a newly discovered waking substance now being used in the trea tment of hypersomnia and narcolepsy. We have shown previously in the cat th at, unlike amphetamine, modafinil induces long-lasting wakefulness (W) with out behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous catecholamines. To further characteri ze the awakening properties of modafinil and current psychostimulants in ex perimental models of hypersomnia, we examined the effect of oral administra tion of placebo, modafinil (5 mg kg(-1)) or amphetamine (1 mg kg(-1)) on th e sleep/wake cycle and power spectral density (PSD) in cats after an 18-h w ater-tank sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both modafinil and amphetamine in duced 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 pla cebo and the PSD during SWS was also increased. Thus, the cumulative time s pent 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 oc currence and evolution of SWS2 or PS, as well as the PSD during SWS, were s imilar 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 co ntrol level, indicating no additional sleep rebound. These results indicate that modafinil is effective against somnolence and hypersomnia and does no t produce a subsequent increase in sleep and suggest that the pharmacologic al profile of modafinil is different from that of amphetamine.