Synergistic effect of estradiol and fluoxetine in young adult and middle-aged female rats in two models of experimental depression

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• 作者：Soledad R¨¦camier-Carballo ; Erika Estrada-Camarena ; Rebeca Reyes ; Alonso Fern¨¢ndez-Guasti
• 关键词：17¦Â-Estradiol ; Fluoxetine ; Forced swimming test ; Chronic mild stress ; Young adult female rats ; Middle-aged female rats
• 刊名：Behavioural Brain Research
• 出版年：2012
• 出版时间：1 August, 2012
• 年：2012
• 卷：233
• 期：2
• 页码：351-358
• 全文大小：864 K

文摘

The antidepressant effect of estrogens combined with antidepressants is controversial: some preclinical data showed that estrogens facilitate the effect of antidepressants in the forced swimming test (FST) in young adult rats, while others failed to find such effect in middle-aged rats in the chronic mild stress (CMS) model. In clinics similar differences were reported and may be due to the compounds, the depression model or type of depression, the experimental design, and the age of the subjects or the women's menopause stage. The objective of this study was to analyze the antidepressant-like effect of the combination of 17¦Â-estradiol (E₂) and fluoxetine (FLX) in young adults (2-4 months) and middle-aged (12-14 months) ovariectomized (OVX) rats in two experimental models: FST and CMS. E₂ (5 and 10 ¦Ìg/rat) and FLX (2.5 and 10 mg/kg) per se dose-dependently reduced immobility in both age groups and, in young adults both compounds increased swimming, whereas in middle-aged rats they increased swimming and climbing. Analysis of the antidepressant-like effect of the combination of suboptimal doses of FLX (1.25 mg/kg) and E₂ (2.5 ¦Ìg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E₂ (2.5 ¦Ìg/rat) with FLX (1.25 mg/kg) augmented relative sucrose intake, but middle-aged rats responded 2 weeks earlier than young adults. These results show that the antidepressant-like effect of the combination of E₂ and FLX in young adult and middle-aged female rats is evidenced in the two animal models of depression: FST and CMS.