Kokras Nikolaos, Pastromas Nikolaos, Porto Tatiany H, Kafetzopoulos Vasilios, Mavridis Theodore, Dalla Christina
Department of Pharmacology,Medical School, University of Athens,Greece.
Int J Neuropsychopharmacol. 2014 Aug;17(8):1307-13. doi: 10.1017/S1461145714000212. Epub 2014 Mar 27.
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.
芳香化酶抑制剂可阻断雄激素向雌激素的转化，用于治疗绝经后激素反应性乳腺癌，最近也用于绝经前女性。我们研究芳香化酶抑制后雌激素合成减少是否会导致处于发情周期的雌性大鼠出现类似抑郁的行为反应。使用强迫游泳试验（FST），我们评估了急性（24小时内注射三次）和持续（7天）给予来曲唑和氟西汀后的反应。急性芳香化酶抑制可减少FST中的不动时间，表明其具有抗抑郁潜力。相反，持续的芳香化酶抑制并未显示出这种抗抑郁潜力。急性来曲唑治疗后，FST中抑郁行为的减少与睾酮升高有关，但有趣的是，孕酮解释了游泳行为的增加。目前的研究结果可能对接受芳香化酶抑制剂治疗的女性，尤其是绝经前女性，以及性腺激素在抑郁症状表达和抗抑郁反应中的作用具有潜在意义。
