title: Acute but not sustained aromatase inhibition displays antidepressant properties.
abstract: Aromatase inhibitors block the conversion of androgens to oestrogens and are used for the treatment of hormone-responsive breast cancer in menopause and recently also in premenopausal women. We investigate whether decreased oestrogen synthesis following aromatase inhibition leads to a depressive-like behavioural response in cycling female rats. Using the forced swim test (FST) we estimate the response of acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine administration. Acute aromatase inhibition decreases immobility duration in the FST, indicating its antidepressant potential. Instead, sustained aromatase inhibition did not show such antidepressant potential. Testosterone elevation associates with the decreased depressive behaviour in the FST following acute letrozole treatment, but interestingly progesterone explains the increased swimming behaviour. Present findings may have potential implications for women treated with aromatase inhibitors, especially before menopause, as well as for the role of gonadal hormones in the expression of depressive symptoms and antidepressant response.
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kokras
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Pastromas
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Tatiany H
authors.initials: TH
authors.lastname: Porto
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Kafetzopoulos
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Theodore
authors.initials: T
authors.lastname: Mavridis
authors.affiliation: Department of Pharmacology,Medical School, University of Athens,Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Dalla
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000097:blood; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D046353:Immobility Response, Tonic / Q000187:drug effects*; D000077289:Letrozole; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D005473:Fluoxetine; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D000077289:Letrozole