effects of adenosine a2a receptor agonist and antagonist on cere-bellar nuclear factor-kbexpression preceded by mdma toxicity

Authors

fatemeh kermanian department of anatomy, school of medicine, alborz university of medical sciences, karaj, iran.سازمان اصلی تایید شده: دانشگاه علوم پزشکی البرز (alborz university of medical sciences)

mansoureh soleimani cellular and molecular research center, department of anatomy, iran university of medical sciences (iums), tehran, iran.سازمان اصلی تایید شده: دانشگاه علوم پزشکی ایران (iran university of medical sciences)سازمان های دیگر: cellular and molecular research center

bagher pourheydar neurophysiology research center, department of anatomy, urmia university of medical sciences, urmia, iran.سازمان اصلی تایید شده: دانشگاه علوم پزشکی ارومیه (urmia university of medical sciences)سازمان های دیگر: neurophysiology research center

alireza samzadeh-kermani chemistry department, faculty of sciences, zabol university, zabol, iran.سازمان اصلی تایید شده: دانشگاه زابل (zabol university)

abstract

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.

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Journal title:
medical journal of islamic republic of iran

جلد ۲۸، شماره ۱، صفحات ۷۹۳-۸۰۳

Keywords
[ ' n ' , ' m e t h y l ' , 3 , 4 , ' m e t h y l e n e d i o x y a m p h e t a m i n e ( m d m a ) ' , ' a d e n o s i n e ' , ' n u c l e a r f a c t o r ' , ' k b ' , ' c e r e b e l l u m . ' ]

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