Modafinil Induces Wakefulness Without Intensifying Motor Activity or Subsequent Rebound Hypersomnolence in the Rat

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