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The Effect of 5-Ht4 Serotonin Receptors in the Ca3 Hippocampal Region on D-Ap5-Induced Anxiolytic-Like Effects: Isobolographic Analyses Publisher Pubmed



Charousaei A1 ; Nasehi M2 ; Babapour V1 ; Vaseghi S2, 3 ; Zarrindast MR3, 4, 5
Authors
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Authors Affiliations
  1. 1. Department of Physiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  2. 2. Cognitive and Neuroscience Research Center (CNRC), Amir-Almomenin Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  3. 3. Department of Cognitive Neuroscience, Institute for Cognitive Science Studies (ICSS), Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Neuroendocrinology, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

Source: Behavioural Brain Research Published:2021


Abstract

Increasing evidence shows the close relationship between hippocampal glutamatergic and serotonergic systems through the modulation of behavioral responses. This study aimed to investigate the possible involvement of 5-HT4 receptors in the CA3 hippocampal region in anxiolytic-like effects induced by D-AP5 (a competitive antagonist of the glutamate NMDA [N-Methyl-D-aspartate] receptor). Male Wistar rats were placed in the elevated plus maze (EPM) apparatus that is used to assess anxiety-related behaviors, and the percentages of open arm time (%OAT) and open arm entries (%OAE) which are associated with anxiety-related behaviors were measured. The close arm entries (CAE) which is correlated with locomotor activity was also evaluated. The results showed that, intra-CA3 injection of D-AP5 (0.4 μg/rat), RS67333 (1.2 μg/rat; a 5-HT4 receptor agonist), and RS23597-190 (1.2 μg/rat; a 5-HT4 receptor antagonist) increased %OAT and %OAE, indicating the anxiolytic-like effect of these drugs. Also, only RS23597-190 (1.2 μg/rat) decreased CAE. Intra-CA3 injection of sub-threshold dose of RS67333 (0.012 μg/rat) or RS23597-190 (0.012 μg/rat), 5 min before the injection of D-AP5 (0.2 μg/rat) increased %OAT, indicating potentiating the anxiolytic-like effect of D-AP5. The isobolographic analyses also showed the additive or synergistic anxiolytic-like effect of intra-CA3 co-administration of D-AP5 with RS67333 or RS23597-190, respectively. In conclusion, CA3 5-HT4 receptors are involved in D-AP5-induced anxiolytic-like behaviors in rats. © 2020
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