Effects of chronic sodium alendronate on depression and anxiety in a menopausal experimental model

Abstract

Objective: During menopause, lower levels of estrogen may induce bone resorption as well as anxiety and depression. Bisphosphonates represent the first choice in the treatment of osteoporosis and no data are available concerning their effects on comorbid behavior alterations. Therefore, in this study, we evaluated the effects of chronic alendronate (1 mg/kg/day) on depression and anxiety in an experimental animal model of menopause.

Methods: Female Wistar rats were ovariectomized or sham operated at 6-7 months of age. Two weeks after surgery, rats were randomized into four treatment (24 consecutive weeks) groups: (1) vehicle-treated SHAM group, (2) alendronate-treated SHAM group, (3) vehicle-treated ovariectomized group, and (4) alendronate-treated ovariectomized group. After treatment, we evaluated both depressive- and anxiety-like behavior through forced swimming test (FST) and open-field test (OF). Finally, the inverted screen test was used to assess the incapacitating effects of ovariectomy in rats.

Results: We documented a significant and time-related increase in immobility times and in anxiety-like behavior in rats with ovariectomy in comparison to control sham group. Alendronate at 3 months, but not at 6 months, significantly decreased both immobility time and anxiety levels, but it significantly increased motor performance. Using the Pearson's test, we documented a significant correlation between behavior and motor performance.

Conclusion: Despite the apparent effects of alendronate on animal behavior, in our experiments, such effects seem to be mediated by an increase in motor performance.

Keywords: Alendronate; Anxiety; Menopause; Mood disorders; Osteoporosis.