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 (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days 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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Acknowledgements
This work was carried out in UGC-SAP assisted Neurobehavioral Pharmacology Laboratory. We thank M. Raj for helping in arranging carbidopa sample from Shodhana Laboratories, Hyderabad. Special thanks to Dr. Bibhu Prasad Panda, for permission to work in Pharmaceutical Biotechnology Laboratory (Jamia Hamdard). The work was supported by fellowship from AICTE (GPAT).
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Wadhwa, R., Kumar, M., Paudel, Y.N. et al. Effect of escitalopram and carbidopa on bone markers in Wistar rats: a preliminary experimental study. J Bone Miner Metab 37, 36–42 (2019). https://doi.org/10.1007/s00774-018-0908-1
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DOI: https://doi.org/10.1007/s00774-018-0908-1