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Adenosine A2a receptors activate Nuclear Factor-Kappa B (NF-κB) in rat hippocampus after exposure to different doses of MDMA

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Abstract

MDMA (3,4-methylenedioxy-N-methamphetamine) as an empathogenic drug causes neurotoxicity although the mechanisms have not been fully elucidated. The A2a adenosine receptor modulates the reinforcement efficacy and neurotoxicity of MDMA. A2a receptor activation inhibits Nuclear Factor-Kappa B (NF-κB) activation and nuclear translocation by a known mechanism. In the present study, we aimed to compare the NF-κB activity level in rat hippocampus between two doses of MDMA exposure (10 and 20 mg /kg) using either A2aR agonist (CGS) or A2aR antagonist (SCH). Adult male Sprague-Dawley rats were subjected to MDMA followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03 mg/kg) injection. The hippocampi were then removed for western blot and RTPCR analyses. Administration of MDMA dose-dependently increased the expression of NF-κB both at mRNA and protein levels. We also found that administration of CGS following MDMA significantly increased the NF-κB expression especially in MDMA 20 +CGS group. By contrast, administration of the A2a-R antagonist SCH resulted in a dose-dependent decrease in NF-κB mRNA and protein. Our study results revealed that MDMA has powerful detrimental effects on expression of NF-κB in a dose-dependent manner. On the other hand, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-κB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran

    Fatemeh Kermanian, Ali Reza Ebrahimzadeh Bideskan, Javad Hami & Hossein Haghir

  2. Cellular & Molecular Research Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Mehdi Mehdizadeh & Mansooreh Soleimani

  3. Department of Anatomical Sciences, Tehran University of Medical Sciences (TUMS), Tehran, Iran

    Mehdi Mehdizadeh

  4. Department of Anatomy, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Javad Hami

  5. Hazrat Rasoul Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Hamed Kheradmand

  6. Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Hossein Haghir

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  1. Fatemeh Kermanian
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Kermanian, F., Mehdizadeh, M., Soleimani, M. et al. Adenosine A2a receptors activate Nuclear Factor-Kappa B (NF-κB) in rat hippocampus after exposure to different doses of MDMA. Mol. Cell. Toxicol. 10, 59–66 (2014). https://doi.org/10.1007/s13273-014-0007-x

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