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Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion

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Abstract

Tropisetron and Granisetorn are 5-HT3 antagonists with antiemetic effects. Tropisetron also has a partial agonistic effect on alpha-7 nicotinic acetylcholine receptors (α7 nAChRs). On the other hand, chronic cerebral hypoperfusion (CCH) attenuates cerebral blood flow and impairs cognitive functions. The goal of this study was to investigate the effect of Tropisetron and Granisetron on CCH-induced spatial memory impairment in rats. Forty-eight male Wistar rats were used in this study. 2-VO surgery was done to induce CCH and Radial Eight Arm Maz apparatus was used to evaluate spatial memory (working and reference memory). Tropisetron was injected intraperitoneally at the doses of 1 and 5 mg/kg, and Granisetron was injected intraperitoneally at the dose of 3 mg/kg. Dorsal hippocampal (CA1) neurons count, Interleukin 6 (IL-6) serum level, and serotonin-reuptake transporter (SERT) gene expression were also evaluated. The results showed, CCH impaired working and reference memory, increased IL-6 serum level, and decreased CA1 neurons and SERT expression. Tropisetron at the dose of 5 mg/kg restored all the effects of CCH. However, Granisetron did not restore CCH-induced memory impairment. Furthermore, Granisetron had no effect on IL-6. While, it increased SERT expression and CA1 neurons. In conclusion, Tropisetron but not Granisetron, ameliorated spatial memory impairment induced by CCH. We suggested conducting more detailed studies investigating the role of serotonergic system (5-HT3 receptors and serotonin transporters) and also α7 nAChRs in the effects of Tropisetron.

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Acknowledgements

Institute for Cognitive Science Studies (ICSS), Tehran, Iran, provided all animal samples and tools needed in this research.

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Authors and Affiliations

  1. Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran

    Ashkan Divanbeigi, Salar Vaseghi & Mohammad-Reza Zarrindast

  2. Scientific Research Committee, Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ashkan Divanbeigi

  3. Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, P.O. Box 13145-784, Tehran, Iran

    Mohammad Nasehi, Salar Vaseghi & Mohammad-Reza Zarrindast

  4. Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran

    Sepideh Amiri

  5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad-Reza Zarrindast

  6. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad-Reza Zarrindast

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AD and SA collected animal data. SV wrote the manuscript, analyzed data, and managed the literature search. MN and MRZ designed the study. All authors have approved the final manuscript.

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Divanbeigi, A., Nasehi, M., Vaseghi, S. et al. Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion. Neurochem Res 45, 2631–2640 (2020). https://doi.org/10.1007/s11064-020-03110-2

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