Modafinil decreases hypersomnolence in the English bulldog, a natural animal model of sleep-disordered breathing.

ABSTRACT

The English bulldog is a natural model of sleep-disordered breathing (SDB). This condition is marked by 1) hypersomnolence and 2) disordered breathing episodes that are most frequent and severe during rapid eye movement (REM) sleep. Modafinil has been found to increase arousal levels in animals and decrease excessive daytime sleepiness in humans. Therefore, in this study we focused mainly on the effects of the drug on total sleep time and sleep latency and secondarily assessed its effect on REM SDB. Five English bulldogs were implanted with subcutaneous electroencephalographic/electrooculographic (EEG/EOG) electrodes and instrumented with respiratory oscillation belts to measure abdominal and rib cage movements and an ear oximeter to measure saturation. The dogs were studied for approximately 8 hours each subsequent day on two consecutive days. On the first day, they received the vehicle dimethyl sulfoxide (DMSO) i.v. as a control. On the following day they received 10 mg/kg body weight of modafinil i.v. dissolved in the DMSO vehicle. Our findings indicate that modafinil significantly alleviates hypersomnolence (p < 0.05) in the bulldog, as evidenced by dramatically decreased mean total sleep time (from a control value of 50.5% to 8.3% with the drug) and increased mean sleep latency (from a control value of 71.0 minutes to a value of 346.6 minutes with the drug). We obtained limited data on the effect of modafinil on SDB because the drug either greatly diminished or entirely eradicated REM sleep in all five dogs.