Abstract

In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0mg/kg, p.o.) and carbidopa (10mg/kg, p.o.) were administered daily for 40days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined. Our results indicated that escitalopram adversely affected bone as indicated by reduced bone formation and enhanced bone resorption. Further, the effects of escitalopram on bone formation were possibly mediated through gut serotonin while the mechanisms responsible for effects on resorption seem unrelated to gut serotonin. The promising effects of carbidopa on bone formation, as observed in our study, open up exciting possibilities for this drug requiring further investigations.

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