|
KMID : 1034820140100010059
|
|
Molecular & Cellular Toxicology
2014 Volume.10 No. 1 p.59 ~ p.66
|
|
|
Adenosine A2a receptors activate Nuclear Factor-Kappa B (NF-κB) in rat hippocampus after exposure to different doses of MDMA
|
|
Kermanian Fatemeh
Mehdizadeh Mehdi
Soleimani Mansooreh
Bideskan Ali Reza Ebrahimzadeh
Hami Javad
Kheradmand Hamed
Haghir Hossein
|
|
|
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.
|
|
|
KEYWORD
|
|
|
MDMA, NF-κB, A2a receptor, CGS, SCH
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|