Medical Journal of The Islamic Republic of Iran (MJIRI)

  Background :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-kBfamilyof 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 forcresyl-violet 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.