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NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study

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Abstract

Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-d-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers. The medial prefrontal cortex (mPFC), lateral prefrontal cortex (lPFC), and orbitofrontal cortex (OFC) were dissected from the brain of 101 drug addicts brains and were compared with the brains of non-addicts (N = 13). Western blotting technique was used to show the alteration in NMDAR subunits level. Data obtained using Western blotting technique showed a significant increase in the level of GluN1 and GluN2B, but not in GluN2A subunits in all the three regions (mPFC, lPFC, and OFC) of men whom suffered from addiction as compared to the appropriate controls. These findings showed a novel role for GluN1, GluN2B subunits, rather than the GluN2A subunit of NMDARs, in the pathophysiology of addiction and suggested their role in the drug-induced plasticity of NMDARs.

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Acknowledgements

The authors acknowledge the grant support of the legal medicine research center.

Author information

Author notes

  1. Hamidreza Daneshparvar and Mitra-Sadat Sadat-Shirazi equal contribution.

Authors and Affiliations

  1. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran

    Hamidreza Daneshparvar

  2. Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, P.O.Box: 13145-784, Iran

    Mitra-Sadat Sadat-Shirazi, Monir Fekri, Nasim Vousooghi & Mohammad-Reza Zarrindast

  3. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mitra-Sadat Sadat-Shirazi & Nasim Vousooghi

  4. Cognitive and Neuroscience research Center (CNRC), Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran

    Solmaz Khalifeh

  5. Legal Medicine Center, Tehran, Iran

    Ali Ziaie

  6. Department of Periodontics, Tehran Dental Branch, Islamic Azad University, Tehran, Iran

    Nasrin Esfahanizadeh

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

    Mohammad-Reza Zarrindast

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  1. Hamidreza Daneshparvar
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Correspondence to Mohammad-Reza Zarrindast.

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Daneshparvar, H., Sadat-Shirazi, MS., Fekri, M. et al. NMDA receptor subunits change in the prefrontal cortex of pure-opioid and multi-drug abusers: a post-mortem study. Eur Arch Psychiatry Clin Neurosci 269, 309–315 (2019). https://doi.org/10.1007/s00406-018-0900-8

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  • DOI: https://doi.org/10.1007/s00406-018-0900-8

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