title: Effects of adenosine A2a receptor agonist and antagonist on hippocampal nuclear factor-kB expression preceded by MDMA toxicity.
abstract: There is an abundance of evidence showing that repeated use of 3,4-methlylenedioxymethamphetamine (MDMA; ecstasy) is associated with brain dysfunction, memory disturbance, locomotor hyperactivity, and hyperthermia. MDMA is toxic to both the serotonergic neurons and dopaminergic system. Adenosine is an endogenous purine nucleoside with a neuromodulatory function in the central nervous system. Nuclear factor kappa-B (NF-kB) plays a pivotal role in the initiation and perpetuation of an immune response by triggering the expression of major inflammatory mediators such as cytokines, chemokines, and adhesion molecules. Here, we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Male Sprague-Dawley rats were injected to MDMA (10 mg/kg) followed by intraperitoneal injection of either CGS or SCH (0.03 mg/kg each) to animals. The hippocampi were then removed for western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results show that administration of CGS following MDMA significantly elevated the NF-kB expression both at mRNA and protein levels. By contrast, administration of the A2a-R antagonist SCH resulted in a decrease in the NF-kB levels. Taken together, these results indicate that, co-administration of A2a agonist (CGS) can protect against MDMA neurotoxic effects by increasing NF-kB expression levels; suggesting a potential application for protection against the neurotoxic effects observed in MDMA users.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. kermanian_s@yahoo.com
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Kermanian
authors.forename: Mansooreh
authors.initials: M
authors.lastname: Soleimani
authors.forename: Alireza
authors.initials: A
authors.lastname: Ebrahimzadeh
authors.forename: Hossein
authors.initials: H
authors.lastname: Haghir
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mehdizadeh
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000502:physiology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D016328:NF-kappa B; D043705:Receptor, Adenosine A2A; D018817:N-Methyl-3,4-methylenedioxyamphetamine