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The Role of Lateral Habenula Nmda Receptors in Tramadol-Induced Conditioning Publisher Pubmed



Hajikarimhamedani A1 ; Heidari A1 ; Sadatshirazi MS2 ; Mahboubi S2 ; Raminfard S3 ; Khalifeh S4 ; Zarrindast MR2, 4, 5
Authors
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Authors Affiliations
  1. 1. Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Iran
  2. 2. Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Iran
  3. 3. Advanced Diagnostic and Interventional Radiology Research Center (ADIR), Tehran University of Medical Sciences, Iran
  4. 4. Cognitive and Neuroscience Research Center (CNRC), Tehran Medical Sciences, Amir-Almomenin Hospital, Islamic Azad University, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Behavioural Pharmacology Published:2023


Abstract

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 214μg/rat) and antagonist (D-AP5, 0.1, 0.5, 114μg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-Administration of NMDA (0.514μg/rat) with tramadol (4m/kg) reduced preference score, while co-Administration of D-AP5 (0.514μg/rat) with a non-effective dose of tramadol (1m/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse. © 2023 Lippincott Williams and Wilkins. All rights reserved.
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