5 alpha-pregnane-3 alpha, 21-diol-20-one (THDOC) attenuates mild stress-induced increases in plasma corticosterone via a non-glucocorticoid mechanism: comparison with alprazolam.
5 alpha-Pregnane-3 alpha,21-diol-20-one (THDOC; 5 mg/kg) and the triazolobenzodiazepine alprazolam (1 mg/kg) attenuated mild stress-induced increases in plasma corticosterone concentrations via GABAergic mechanisms. Unlike alprazolam, THDOC failed to decrease corticotropin-releasing factor (CRF) concentrations in the locus ceruleus. While THDOC may plausibly act via endogenous GABAergic mechanisms to reduce stress-induced endocrine and behavioral responses that are likely mediated in part by CRF neurons, these preliminary findings suggest that, at the dose and time point studied, THDOC does not identically mimic the actions of alprazolam, another drug which potentiates GABAergic activity.
Owens
M J
MJ
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Ritchie
J C
JC
Nemeroff
C B
CB
D000525:Alprazolam / Q000494:pharmacology*; D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013312:Stress, Physiological / Q000503:physiopathology*
D003900:Desoxycorticosterone; C009413:tetrahydrodeoxycorticosterone; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone; D000525:Alprazolam