The effects of the neuroactive steroid 3 alpha,5 alpha-THDOC on sleep in the rat.
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.
Müller-Preuss
Peter
P
Max-Planck-Institute of Psychiatry, Kraepelinstrasse 2-10, D-80804 Munich, Germany.
Rupprecht
Rainer
R
Lancel
Marike
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000494:pharmacology / Q000502:physiology; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology* / Q000502:physiology; D011280:Pregnanolone / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects* / Q000502:physiology
D014151:Anti-Anxiety Agents; D012739:Gonadal Steroid Hormones; D018377:Neurotransmitter Agents; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D011280:Pregnanolone