Effects of adenosine A2a receptor agonist and antagonist on cerebellar nuclear factor-kB expression preceded by MDMA toxicity

Kermanian, F and Soleimani, M and Pourheydar, B and Samzadeh Kermani, A and Mohammadzadeh, F and Mehdizadeh, M (2014) Effects of adenosine A2a receptor agonist and antagonist on cerebellar nuclear factor-kB expression preceded by MDMA toxicity. Medical Journal of the Islamic Republic of Iran, 28 (1).

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Abstract

Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic amphetamine analogue used recreationally to obtain an enhanced affiliated emotional response. MDMA is a potent monoaminergic neurotoxin with the potential of damage to brain neurons. The NF-kB family of proteins are ubiquitously expressed and are inducible transcription factors that regulate the expression of genes involved in disparate processes such as immunity and ingrowth, development and cell-death regulation. In this study we investigated the effects of the A2a adenosine receptor (A2a-R) agonist (CGS) and antagonist (SCH) on NF-kB expression after MDMA administration. Methods: Sixty three male Sprague–Dawley rats were injected to MDMA (10 and 20mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03mg/kg) injection. The cerebellum were then removed forcresylviolet staining, western blot and RT- PCR analyses. MDMA significantly elevated NF-kB expression. Our results showed that MDMA increased the number of cerebellar dark neurons. Results: We observed 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. Conclusion: These results indicated 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.

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