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

• Published in: Behavioural brain research 2012-08, Vol.233 (2), p.351-358
• Main Authors: Récamier-Carballo, Soledad, Estrada-Camarena, Erika, Reyes, Rebeca, Fernández-Guasti, Alonso
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Aging; Analysis of Variance; Animals; Antidepressive Agents, Second-Generation - therapeutic use; Chronic mild stress; Depression - drug therapy; Disease Models, Animal; Drug Synergism; Estradiol - therapeutic use; Female; Fluoxetine; Fluoxetine - therapeutic use; Food Preferences - drug effects; Forced swimming test; Immobility Response, Tonic - drug effects; Middle-aged female rats; Motor Activity - drug effects; Ovariectomy; Rats; Stress, Psychological - drug therapy; Sucrose; Swimming - psychology; Young adult female rats
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2012.05.034

► We compared the effect of E2+FLX in the FST and CMS in young and middle-aged ♀ rats. ► E2 and FLX given alone dose-dependently reduced immobility in both age groups. ► E2+FLX reduced immobility in both ages but the active behavior profile differed. ► E2+FLX increased sucrose intake in both ages with middle-aged responding earlier. 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 17β-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 10μg/rat) and FLX (2.5 and 10mg/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 (1.25mg/kg) and E2 (2.5μg/rat) showed a decrease in immobility and an increase in swimming in both age groups. In the CMS, chronic E2 (2.5μg/rat) with FLX (1.25mg/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.