Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion
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ORIGINAL PAPER
Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion Ashkan Divanbeigi1,2 · Mohammad Nasehi3 · Salar Vaseghi1,3 · Sepideh Amiri4 · Mohammad‑Reza Zarrindast1,3,5,6 Received: 16 May 2020 / Revised: 3 August 2020 / Accepted: 8 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Chronic cerebral hypoperfusion (CCH) · Tropisetron · Granisetron · Spatial memory · Interleukin 6 (IL-6)
Introduction
* Mohammad Nasehi [email protected] 1
Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran
2
Scientific Research Committee, Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3
Cognitive and Neuroscience Research Center (CNRC), Amir‑Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, P.O. Box 13145‑784, Tehran, Iran
4
Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
5
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
6
Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
Bilateral common carotid artery occlusion (2-VO) is used to induce chronic cerebral hypoperfusion (CCH) in rodents [1]. In previous studies, oxidative stres
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