The effects of the neuroactive steroid 3α,5α-THDOC on sleep in the rat

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Abstract
This vehicle-controlled study assessed the sleep effects of the naturally occurring neuroactive steroid 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-THDOC; 7.5 and 15 mg/kg), administered i.p. to rats, and compared them with those of another neuroactive steroid allopregnanolone (15 mg/kg). 3alpha,5alpha-THDOC shortened sleep latency, selectively promoted pre-REMS (a transitional state between non-REMS and REMS) and lengthened the non-REMS episodes dose-dependently. Spectral analysis of the EEG within non-REMS found significant attenuations of low-frequency activity and elevations in the spindle and higher frequency bands. The effects of 3alpha,5alpha-THDOC closely match those of allopregnanolone, indicating a common mechanism of action. Since the sleep changes produced by these steroids resemble the sleep profile of benzodiazepine hypnotics, they are probably caused by a positive allosteric modulation of GABAA receptor function.