The Role of The A2A Receptor in Cell Apoptosis Caused by MDMA

(Pages: 231-236)
Mansooreh Soleimani, Ph.D., 1Majid Katebi, Ph.D., 2Akram Alizadeh, M.Sc., 3Farzaneh Mohammadzadeh, M.Sc., 4Mehdi Mehdizadeh, Ph.D., 1,4,*
* Corresponding Address: P.O.Box: 1419954161 Department of Anatomy Tehran University of Medical Sciences Tehran Iran
Any use, distribution, reproduction or abstract of this publication in any medium, with the exception of commercial purposes, is permitted provided the original work is properly cited This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Soleimani Mansooreh, Katebi Majid, Alizadeh Akram, Mohammadzadeh Farzaneh, Mehdizadeh Mehdi. The Role of The A2A Receptor in Cell Apoptosis Caused by MDMA. Cell J. 2012; 14(3): 231-236.



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.

Materials and Methods:

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.