الفهرس | Only 14 pages are availabe for public view |
Abstract Introduction: The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressant drugs; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17Ý-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Methods: Female wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated for 30 days with escitalopram (10 mg/kg/day, i.p) alone or with four doses of 17b-estradiol (40 æg/kg, s.c) given prior to the behavioral tests. Results: Administration of 17b-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17b-estradiol augmented the modulatory effects of escitalopram on the hippocampal contents of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin 1Areceptor, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the histopathological architecture of the hippocampus. The antidepressant effect of 17b-estradiol was abolished by pretreatment with intracellular estrogen receptors antagonist, tamoxifen |