الفهرس 
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Abstract
Background: Depression and osteoporosis secondary to estrogen deficiency in postmenopausal women have been traditionally treated with HRT. The increased risk of cancer associated with HRT prompted the use of SERM for management of postmenopausal osteoporosis. Whether SERMs might also benefit postmenopausal depression is debatable.
Aim of the work: The present study was conducted using the rat model of ovariectomy to investigate the possible beneficial effects of the SERM raloxifene alone and in combination with the SSRI fluoxetine on the depressive like behavior induced by ovariectomy as well as on several biochemical changes pertaining to the different hypothesis of depression. The impact of the test drugs on the bone changes induced by ovariectomy was also investigated.
Methodology: Rats were divided into 5 groups (12 rats each):Sham operated, OVX, OVX-Fluoxetine (10 mg/kg), OVX-raloxifene (1mg/kg) and OVX - Fluoxetine + Raloxifene treated groups. 4 weeks following ovariectomy, drugs were given, orally daily for another 4 weeks.
Results: Ovariectomy induced behavioral changes in rats (significant increase in immobility time in FST, and decrease in active interaction time in SIT and in locomotor activity in OFT. These changes were associated with increase in oxidative stress (increased serum MDA level and decreased serum and hippocampus GSH) and in hippocampus TNFα as well as a reduction in hippocampus BDNF. Rats treated with either fluoxetine or raloxifene, exhibited reversal of behavioral changes induced by ovariectomy together with amelioration of the changes in TNFα, oxidative stress and BDNF. Combination of raloxifene with fluoxetine induced a further improvement in these parameters. OVX rats exhibited increase in serum hydroxyproline (bone resorption marker) and histological changes in femur bone (reduction in outer cortical bone thickness and trabecular bone volume). These changes were aggravated by fluoxetine and ameliorated by combination with raloxifene.
Conclusion: Raloxifene potentiates the effects of fluoxetine against ovariectomy- induced behavioral changes and protects against the histo-pathological changes in femur bone, associated with ovariectomy, or those induced by fluoxetine. These findings suggest that combination of raloxifene with SSRIs, in post-menopausal women might offer the double benefit of potentiating the antidepressant effects of SSRIs while protecting against their negative impact on bone.