Trilostane exerts antidepressive effects among wild-type, but not estrogen receptor [beta] knockout mice.
Women with estrogen receptor (ER) positive breast cancer, who are treated with the ER blocker, tamoxifen, have an increased risk of depression. Trilostane, a 3b-hydroxysteroid dehydrogenase inhibitor, is now being used to treat tamoxifen-insensitive breast cancer. In-vitro assays show that trilostane may have actions through ERb. Results of in-vivo research shows that actions at ERb may underline some antidepressant effects of estrogen. We hypothesized that trilostane may exert antidepressive effects in the forced swim in part due to actions through ERb. Trilostane (25 mg/kg, intraperitoneally), compared with vehicle, had significant antidepressant-like effects but only when administered to wild-type, not ERb knockout, mice. Thus, actions of trilostane through ERb may underlie some of its antidepressant-like effects.
Koonce
Carolyn J
CJ
Department of aPsychology, University at Albany-SUNY, Albany, New York 12222, USA.
Walf
Alicia A
AA
Frye
Cheryl A
CA
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D011280:Pregnanolone / Q000378:metabolism; D011863:Radioimmunoassay; D013550:Swimming; D013997:Time Factors
D000928:Antidepressive Agents; D047629:Estrogen Receptor beta; D013196:Dihydrotestosterone; D011280:Pregnanolone; C009954:trilostane; D003345:Corticosterone