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The Bidirectional Effect of Prelimbic 5-Hydroxytryptamine Type-4 (5-Ht4) Receptors on Acpa-Mediated Aversive Memory Impairment in Adult Male Sprague-Dawley Rats Publisher



Ahmadimahmoodabadi N1, 2 ; Emamghoreishi M3 ; Nasehi M4 ; Zarrindast MR1, 4, 5, 6, 7
Authors
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Authors Affiliations
  1. 1. Institute for Cognitive Science Studies, Tehran, Iran
  2. 2. Department of Basic Sciences, Campus of Shahid Bahonar, Farhangian University of Shiraz, Shiraz, Iran
  3. 3. Department of Pharmacology, School of Medicine, Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
  4. 4. Cognitive and Neuroscience Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  5. 5. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. School of Cognitive Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran

Source: Iranian Journal of Basic Medical Sciences Published:2021


Abstract

Objective(s): This study aimed at investigating the effect of serotonergic 5-HT4 receptor agonist/ antagonist on memory consolidation deficit induced by ACPA (a potent, selective CB1 cannabinoid receptor agonist) in the pre-limbic (PL) cortex. Materials and Methods: We used the step-through passive avoidance test to evaluate memory consolidation of male Sprague-Dawley (SD) rats. Bilateral post-training microinjections of the drugs were done in a volume of 0.6 μl/rat into the PL area (0.3 μl per side). Results: The results showed a significant interaction between RS67333 hydrochloride (5-HT4 receptor agonist) or RS23597-190 hydrochloride (5-HT4 receptor antagonist) and ACPA on consolidation of aversive memory. RS67333 hydrochloride (0.5 μg/rat) enhanced consolidation of memory and its co-administration at the ineffective dose of 0.005 μg/rat with ineffective (0.001 μg/rat) or effective (0.1 μg/rat) doses of ACPA improved and prevented impairment of memory caused by ACPA, respectively. In other words, RS67333 had a bidirectional effect on ACPA-caused amnesia. While RS23597-190 hydrochloride had no effect on memory at the doses used (0.005, 0.01, 0.1, or 0.5 μg/rat); but its concomitant use with an effective dose of ACPA (0.1 μg/rat) potentiated amnesia. None of the drugs had an effect on locomotor activity. Conclusion: This study revealed that activation or deactivation of the 5-HT4 receptors in the PL may mediate the IA memory impairment induced by ACPA indicating a modulatory role for the 5-HT4 serotonergic receptors. © 2021 Mashhad University of Medical Sciences. All rights reserved.
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