Differential effects of midazolam and zolpidem on sleep-wake states and epileptic activity in WAG/Rij rats.

Hypnotic drugs are known to possess antiepileptic activity. Therefore, the effects of the benzodiazepine hypnotic midazolam (10 mg/kg) and the novel imidazopyridine hypnotic zolpidem (10 mg/kg) on sleep-wake states and on the number of spike-wave discharges were evaluated in WAG/Rij rats. Rats of this strain are considered to be a model for generalized absence epilepsy. Animals were implanted with chronic monopolar EEG electrodes and, after recovery from surgery, the EEG was recorded for 6 h during the dark period on 3 consecutive days. Sleep recordings were analyzed using Hjorth's parameters and number and duration of spike-wave discharges were visually determined. It was found that both drugs facilitated nonREM sleep at the cost of wakefulness. Both hypnotics also reduced the number and duration of spike-wave discharges. The initial decrease after midazolam, however, was followed by a rebound reflecting a poorer quality of vigilance expressed as an increase in spike-wave discharges. The strong antiabsence activity of zolpidem mimics that of midazolam and is well correlated with their equipotent hypnotic action and anticonvulsant effect in the isoniazid test.