Molecular & Cellular Toxicology

, Volume 10, Issue 1, pp 59–66 | Cite as

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

  • Fatemeh Kermanian
  • Mehdi Mehdizadeh
  • Mansooreh Soleimani
  • Ali Reza Ebrahimzadeh Bideskan
  • Javad Hami
  • Hamed Kheradmand
  • Hossein Haghir
Original Paper

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.

Keywords

MDMA NF-κB A2a receptor CGS SCH 

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Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Fatemeh Kermanian
    • 1
  • Mehdi Mehdizadeh
    • 2
    • 3
  • Mansooreh Soleimani
    • 2
  • Ali Reza Ebrahimzadeh Bideskan
    • 1
  • Javad Hami
    • 1
    • 4
  • Hamed Kheradmand
    • 5
  • Hossein Haghir
    • 1
    • 6
  1. 1.Department of Anatomy and Cell Biology, School of MedicineMashhad University of Medical Sciences (MUMS)MashhadIran
  2. 2.Cellular & Molecular Research CenterTehran University of Medical Sciences (TUMS)TehranIran
  3. 3.Department of Anatomical SciencesTehran University of Medical Sciences (TUMS)TehranIran
  4. 4.Department of Anatomy, School of MedicineBirjand University of Medical SciencesBirjandIran
  5. 5.Hazrat Rasoul HospitalTehran University of Medical SciencesTehranIran
  6. 6.Medical Genetic Research Center (MGRC), School of MedicineMashhad University of Medical SciencesMashhadIran

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