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

Soleimani, Mansooreh. and Katebi, Majid. and Alizadeh, Akram. and Mohammadzadeh, Farzaneh. and Mehdizadeh, Mehdi. (2012) The Role of The A2A Receptor in Cell Apoptosis Caused by MDMA. Cell Journal (Yakhteh), 14 (3).

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Abstract

OBJECTIVE: 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. RESULTS: 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). CONCLUSION: 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.

Item Type: Article
Uncontrolled Keywords: Adenosine Receptor; Agonist of A2A Receptor; Antagonist of A2A Receptor; Ecstasy or MDMA; Neurotoxicity
Subjects: WL Nervous system
QU Biochemistry
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: zahra bagheri .
Date Deposited: 28 Nov 2017 06:56
Last Modified: 28 May 2018 06:00
URI: http://eprints.skums.ac.ir/id/eprint/6451

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