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The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Iranian Neuroscience Society
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683689/ https://www.ncbi.nlm.nih.gov/pubmed/29158882 http://dx.doi.org/10.18869/nirp.bcn.8.4.317 |
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author | Bakhshayesh, Masoomeh Golab, Fereshteh Kermanian, Fatemeh Mehdizadeh, Mehdi Katebi, Amir Reza Soleimani, Mansooreh Mohammadzadeh, Farzaneh Shabani, Ronak Movahed, Elham Katebi, Majid |
author_facet | Bakhshayesh, Masoomeh Golab, Fereshteh Kermanian, Fatemeh Mehdizadeh, Mehdi Katebi, Amir Reza Soleimani, Mansooreh Mohammadzadeh, Farzaneh Shabani, Ronak Movahed, Elham Katebi, Majid |
author_sort | Bakhshayesh, Masoomeh |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5683689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Iranian Neuroscience Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-56836892017-11-20 The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat Bakhshayesh, Masoomeh Golab, Fereshteh Kermanian, Fatemeh Mehdizadeh, Mehdi Katebi, Amir Reza Soleimani, Mansooreh Mohammadzadeh, Farzaneh Shabani, Ronak Movahed, Elham Katebi, Majid Basic Clin Neurosci Research Paper 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. Iranian Neuroscience Society 2017 /pmc/articles/PMC5683689/ /pubmed/29158882 http://dx.doi.org/10.18869/nirp.bcn.8.4.317 Text en Copyright© 2017 Iranian Neuroscience Society http://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Paper Bakhshayesh, Masoomeh Golab, Fereshteh Kermanian, Fatemeh Mehdizadeh, Mehdi Katebi, Amir Reza Soleimani, Mansooreh Mohammadzadeh, Farzaneh Shabani, Ronak Movahed, Elham Katebi, Majid The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title | The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title_full | The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title_fullStr | The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title_full_unstemmed | The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title_short | The Mediating Role of A(2A) Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat |
title_sort | mediating role of a(2a) adenosine receptors in the mitochondrial pathway of apoptotic hippocampal cell death, following the administration of mdma in rat |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683689/ https://www.ncbi.nlm.nih.gov/pubmed/29158882 http://dx.doi.org/10.18869/nirp.bcn.8.4.317 |
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