Pregnenolone enhances EEG delta activity during non-rapid eye movement sleep in the rat, in contrast to midazolam.

Several endogenous steroids exert their neuroactivity through non-genomic effects and act as potent GABAA receptor-agonists or-antagonists. To examine the influence of the main precursor of these steroids on sleep-wake behaviour, pregnenolone (400 micrograms) was dissolved in oil and administrated s.c. to 8 rats at the beginning of the light period. For comparison, the benzodiazepine midazolam was also injected (3 mg/kg). The effects on the amounts of the vigilance states and on the EEG signals within each state were investigated during 24 hours. Compared to control vehicle, pregnenolone did not significantly affect the duration of the vigilance states. However, delta activity (0.5-4 Hz) within non-rapid eye movement sleep (nonREMS) was enhanced throughout the recording period. Midazolam increased nonREMS, decreased wakefulness and, transiently, also suppressed rapid eye movement sleep (REMS). Spectral analysis of the EEG within nonREMS showed a long lasting reduction in delta and theta activity (4-9 Hz) and a shorter lasting enhancement in the higher frequencies (10-25 Hz). EEG activity within REMS and wakefulness was elevated in the higher frequencies (> or = 10 Hz) during the the first half of the recording period. We conclude that in the rat, the effects of midazolam on EEG activity closely resemble those of benzodiazepines in other mammalian species. The influence of pregnenolone on EEG delta activity within nonREMS indicates that pregnenolone acts as an inverse GABAA-benzodiazepine agonist.