Although its mechanism of action is unknown, Provigil appears to be unlike classic stimulants. We investigated this generality by testing the selectivity of this compound for wake-promoting effects (e.g., relative to locomotor effects) and homeostatic sleep responses after drug-induced waking relative to the prototypical stimulant methamphetamine (METH).
Continuous measures of electroencephalogram (EEG) sleep-wakefulness, locomotor activity (LMA) and body temperature (Tb) were obtained from adult male Wistar rats 3 days before and after treatment with Provigil (30, 100 and 300 mg/kg i.p.), 0.25% methylcellulose (vehicle) or METH (0.5 and 1.0 mg/kg i.p.). Individually housed rats in a 24-h light-dark cycle (LD 12:12) were treated 5 h after lights-on (CT-5).
LMA and Tb were monitored via intraperitoneal telemetry. Sleep-wake stages and LMA were recorded every 10 s, Tb every minute. During the first 3 h post-treatment, Provigil and METH significantly and dose-dependently increased EEG wake time (P < .01 for 30 mg/kg Provigil, all other P < .0001) and wake episode duration.
Although the cumulative increases in wakefulness were statistically equivalent, METH, but not Provigil, produced subsequent rebound hypersomnolence.
At these equipotent wake-promoting doses, Provigil produced the same total amount of REM sleep inhibition but during a longer time than METH. Provigil also increased LMA amount (counts/h, P < .001) and LMA intensity (counts/min awake, P < .001) less than METH. Both rebound hypersomnolence and increased LMA intensity, which are undesirable features in wake-promoting drugs, were not observed after Provigil treatment, and thus further differentiated Provigil from amphetamine-like stimulants.