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-geno mic effects and act as potent GABA, receptor-agonists or -antagonists. To examine the influence of the main precursor of these steroids on s leep-wake behaviour, pregnenolone (400 mu g) 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 sig nals within each state were investigated during 24 hours. Compared to control vehicle, pregnenolone did not significantly affect the duratio n of the vigilance states. However, delta activity (0.5-4 Hz) within n on-rapid eye movement sleep (nonREMS) was enhanced throughout the reco rding 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 i n the higher frequencies (10-25 Hz). EEG activity within REMS and wake fulness was elevated in the higher frequencies (greater than or equal to 10 Hz) during the first half of the recording period. We conclude t hat in the rat, the effects of midazolam on EEG activity closely resem ble those of benzodiazepines in other mammalian species. The influence of pregnenolone on EEG delta activity within nonREMS indicates that p regnenolone acts as an inverse GABA(A)-benzodiazepine agonist.