role of the A2A receptor in cell apoptosis caused by MDMA

ABSTRACT

Ecstasy, also known as 3, 4-methylenedioxymethamphetamine [MDMA], is a psychoactive recreational hallucinogenic substance and a major worldwide recreational drug. There are neurotoxic effects observed in laboratory animals and humans following MDMA use. MDMA causes apoptosis in neurons of the central nervous system [CNS]. Withdrawal signs are attenuated by treatment with the adenosine receptor [A2A receptor]. This study reports the effects of glutamyl cysteine synthetase [GCS], as an A2A receptor agonist, and succinylcholine [SCH], as an A2A receptor antagonist, on Sprague Dawley rats, both in the presence and absence of MDMA. In this experimental study, we used seven groups of Sprague Dawley rats [200-250 g each]. Each group was treated with daily intraperitoneal [IP] injections for a period of one week, as follows i. MDMA [10 mg/kg]; ii. GCS [0.3 mg/kg]; iii. SCH [0.3 mg/kg]; iv. GCS + SCH [0.3 mg/kg each]; v. MDMA [10 mg/kg] + GCS [0.3 mg/kg]; vi. MDMA [10 mg/kg] + SCH [0.3 mg/kg]; and vi. normal saline [1 cc/kg] as the sham group. Bax [apoptotic protein] and Bcl-2 [anti-apoptotic protein] expressions were evaluated by striatum using RT-PCR and Western blot analysis. There was a significant increase in Bax protein expression in the MDMA+SCH group and a significant decrease in Bcl-2 protein expression in the MDMA+SCH group [p<0.05]. A2A receptors have a role in the apoptotic effects of MDMA via the Bax and Bcl-2 pathways. An agonist of this receptor [GCS] decreases the cytotoxcity of MDMA, while the antagonist of this receptor [SCH] increases its cytotoxcity