The influence of subchronic administration of the neurosteroid allopregnanolone on sleep in the rat

The endogenous neurosteroid allopregnanolone has recently been demonstrated to have somnogenic properties that are very similar to those of other agon istic modulators Of GABAA receptors, especially of short-acting benzodiazep ines. Short-acting benzodiazepines are established to rapidly lose their hy pnotic effect upon repeated administration. To investigate the tolerance po tential of allopregnanolone, we assessed sleep-wake behavior in rats during subchronic treatment (once daily for five days) with placebo or 15 mg/kg a llopregnanolone (n = 8 each). The sleep patterns of the placebo and allopre gnanolone group did not differ significantly before and after treatment. Th roughout the entire treatment period the allopregnanolone group exhibited s horter non-rapid eye movement sleep (non-REMS) latencies, prolonged REMS la tencies, longer non-REMS episodes, more pre-REMS and less low-frequency, bu t higher spindle activity in the electroencephalogram (EEG) within non-REMS than the placebo group. The lack of tolerance effects suggests that allopr egnanolone may be an efficacious modulator of sleep-wake behavior over long er time periods than most drugs targeting the benzodiazepine binding site o f the GABAA receptor.