The Mediating Role of A2A Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat

Masoomeh Bakhshayesh; Fereshteh Golab; Fatemeh Kermanian; Mehdi Mehdizadeh; Amir Reza Katebi; Mansooreh Soleimani; Farzaneh Mohammadzadeh; Ronak Shabani; Elham Movahed; Majid Katebi

doi:10.18869/nirp.bcn.8.4.317

The Mediating Role of A_2A Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat

Basic Clin Neurosci. 2017 Jul-Aug;8(4):317-324. doi: 10.18869/nirp.bcn.8.4.317.

Authors

Masoomeh Bakhshayesh¹, Fereshteh Golab¹, Fatemeh Kermanian², Mehdi Mehdizadeh^{1

3}, Amir Reza Katebi⁴, Mansooreh Soleimani^{1

3}, Farzaneh Mohammadzadeh³, Ronak Shabani^{1

3}, Elham Movahed³, Majid Katebi^{1

5}

Affiliations

¹ Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
² Department of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
³ Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
⁴ Department of Educational Psychology, Faculty of Psychology & Educational Sciences, Allameh Tabataba'i University, Tehran, Iran.
⁵ Department of Anatomy, School of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.

Abstract

Introduction: The 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug and a major source of substance abuse, which ultimately leads to sensations of well-being, elation and euphoria, moderate derealization/depersonalization, and cognitive disruptions, as well as intense sensory awareness. The mechanisms involved in memory impairment induced by MDMA are not completely understood.

Methods: The current study used 40 Sprague-Dawley rats, weighted 200 to 250 g. Experiments were performed in four groups, each containing 10 rats. The first group of rats was used as the control, treated with dimethyl sulfoxide (DMSO). The second group was treated with MDMA. The third group was treated with MDMA and CGS (the adenosine A_2A receptor agonist, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine) (CGS 21680) and the fourth group was treated with MDMA and SCH (the A_2A receptor antagonist [7-(2-phenylethyl)-5-amino-2-(2-furyl-) pyrazolo-[4, 3-e]-1, 2, 4 triazolo [1,5-] pyrimidine]) (SCH 58261). The drugs in all groups were administrated intraperitoneally (i.p.) once a day for 7 days. In 5 rats of each group, following perfusion, samples were taken from hippocampi to investigate apoptosis. Accordingly, the samples were stained using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay kit, and studied by light microscopy. In other rats, fresh tissue was also removed to study the expression of bax and bcl-2 by Western blotting technique.

Results: It was observed that the coadministration of MDMA with CGS reduced bax expression and prevented apoptosis of hippocampal cells. The coadministration of MDMA and SCH increased bax expression, and also increased the frequency of hippocampal cell apoptosis.

Conclusion: The results of the current study showed that administration of CGS with MDMA decreased the common side effects associated with MDMA.

Keywords: Adenosine receptor; Agonist of A2A receptor; Antagonist of A2A receptor; Ecstasy or MDMA; Neurotoxicity.