title: The influence of subchronic administration of the neurosteroid allopregnanolone on sleep in the rat.
abstract: The endogenous neurosteroid allopregnanolone has recently been demonstrated to have somnogenic properties that are very similar to those of other agonistic modulators of GABA(A) receptors, especially of short-acting benzodiazepines. Short-acting benzodiazepines are established to rapidly lose their hypnotic effect upon repeated administration. To investigate the tolerance potential of allopregnanolone, we assessed sleep-wake behavior in rats during subchronic treatment (once daily for five days) with placebo or 15 mg/kg allopregnanolone (n = 8 each). The sleep patterns of the placebo and allopregnanolone group did not differ significantly before and after treatment. Throughout the entire treatment period the allopregnanolone group exhibited shorter non-rapid eye movement sleep (non-REMS) latencies, prolonged REMS latencies, longer non-REMS episodes, more pre-REMS and less low-frequency, but higher spindle activity in the electroencephalogram (EEG) within non-REMS than the placebo group. The lack of tolerance effects suggests that allopregnanolone may be an efficacious modulator of sleep-wake behavior over longer time periods than most drugs targeting the benzodiazepine binding site of the GABA(A) receptor.
authors.affiliation: Max-Planck-Institute of Psychiatry, Munich, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Damianisch
authors.forename: R
authors.initials: R
authors.lastname: Rupprecht
authors.forename: M
authors.initials: M
authors.lastname: Lancel
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D008297:Male; D011280:Pregnanolone / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: C028952:allopregnan-20 alpha-ol-3-one; D011280:Pregnanolone