Sleep induction by an adrenal steroid in the rat.
The ring A reduced metabolites of deoxycorticosterone and progesterone, 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) and 3 alpha-hydroxy-5 alpha-dihydroprogesterone (3 alpha-OH-DHP) have been shown to be potent barbiturate-like ligands of the benzodiazepine receptor complex. The former has also been reported to have anxiolytic effects in mice and rats. In the present study, sleep recordings were obtained on rats given 5 and 10 mg/kg of these steroids alone and in combination with flurazepam. THDOC, but not 3 alpha-OH-DHP, had potent dose-dependent sleep-inducing properties and increased nonREM sleep. Flurazepam had similar hypnotic effects and also reduced REM sleep. There were no significant interactions between THDOC and flurazepam, except in the case of REM latency, which tended to increase when the two compounds were given together. In summary, THDOC, a mineralocorticoid metabolite found in brain, has sedative properties and could conceivably play a role in stress responses.
D000818:Animals; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005479:Flurazepam / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011283:Pregnenes / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects
D011283:Pregnenes; C021323:4-pregnene-3 alpha,20 alpha-diol; D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D005479:Flurazepam