en Anatomical Sciences Anatomical Sciences Original Research Original Research <p> <strong> Background </strong>: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. </p><p> <strong> Methods </strong>: 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. </p><p> <strong> Results </strong>: 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. </p><p> <strong> Conclusion </strong>: 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. </p> N-Methyl-3,4-methylenedioxyamphetamine (MDMA), Adenosine , Nuclear factor-kB, Cerebellum. 793 803 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-1569-2&slc_lang=en&sid=1 Fatemeh Kermanian Kermanian92@yahoo.com 200319475328460013803 200319475328460013803 No Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. Mansoureh Soleimani mansourehsoleimani@gmail.com 200319475328460013804 200319475328460013804 No Cellular and Molecular Research Center, Department of Anatomy, Iran University of Medical Sciences (IUMS), Tehran, Iran. Bagher Pourheydar Bagher.pourheydar@gmail.com 200319475328460013805 200319475328460013805 No Neurophysiology Research Center, Department of Anatomy, Urmia University of medical sciences, Urmia, Iran. Alireza Samzadeh-Kermani arsamzadeh@yahoo.com 200319475328460013806 200319475328460013806 No Chemistry Department, Faculty of Sciences, Zabol University, Zabol, Iran. Farzaneh Mohammadzadeh 200319475328460013807 200319475328460013807 No Department of Anatomy,Iran university of medical sciences ,Tehran, Iran. Mehdi Mehdizadeh mehdizadeh.m@iums.ac.ir 200319475328460013808 200319475328460013808 Yes Cellular and Molecular Research Center, Faculty of Advanced Technology in Medicine, Department ofAnatomy, Iran University of Medical Sciences (IUMS), Tehran, Iran.