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Neuroprotective effects of 5-HT3 receptor antagonist ondansetron on morphine withdrawal induced brain edema formation, blood-brain barrier dysfunction, neuronal injuries, glial activation and heat shock protein upregulation in the brain
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Banaras Hindu Univ, Indian Inst Technol, Sch Biomed Engn, Dept Biomat, Varanasi, Uttar Pradesh, India.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2019 (English)In: New Therapeutic Strategies for Brain Edema and Cell Injury / [ed] Sharma, HS Sharma, A, Elsevier, 2019, p. 209-228Chapter in book (Refereed)
Abstract [en]

Morphine withdrawal response is associated with brain edema formation, blood-brain barrier (BBB) disruption, activation of glial cells and heat shock protein (HSP 72kDa) responses in the CNS. Thus, exploration of suitable therapeutic measures is the need of the hour to induce neuroprotection in morphine withdrawal cases. There are reports that 5-HT3-receptor antagonists ondansetron attenuate some of the behavioral changes in morphine-withdrawal symptoms. However, brain protection in morphine withdrawal using pharmacological approaches is still not well known. In present investigation, effect of ondansetron the potent 5-HT3 receptor antagonist on brain edema formation BBB disruption, glial activation and/or HSP response following morphine withdrawal was examined. Rats received ondansetron (1mg or 2mg/kg, s.c) or saline once daily from 2 days before morphine administration (10 mg/kg, s.c. once daily for 10 days) that continued up to 2days after its withdrawal (day 13th). Cessation of morphine on day 11th results in withdrawal symptoms and BBB breakdown to proteins in the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus, brain stem and spinal cord along with activation of glial fibrillary acidic protein (GFAP) and HSP immunoreactivity. In these animals brain edema and neurotoxicity are prominent on day 13th as compared to controls. Ondansetron treatment significantly reduced withdrawal symptoms on the day 13th in a dose dependent manner and attenuated BBB breakdown, edema formation, GFAP and HSP expression and neuronal injuries. These observations are the first to show that ondansetron is neuroprotective following morphine withdrawal indicating an important role of 5-HT3 receptors in psychostimulants abuse.

Place, publisher, year, edition, pages
Elsevier, 2019. p. 209-228
Series
International Review of Neurobiology, ISSN 0074-7742 ; 146
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-401913DOI: 10.1016/bs.irn.2019.06.011ISI: 000501592100008PubMedID: 31349928ISBN: 978-0-12-816754-0 (print)OAI: oai:DiVA.org:uu-401913DiVA, id: diva2:1385166
Funder
Swedish Research Council, 2710Available from: 2020-01-13 Created: 2020-01-13 Last updated: 2020-01-13Bibliographically approved

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Sharma, ArunaSharma, Hari Shanker

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