The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study.
Fatemeh Kermanian, Mehdi Mehdizadeh, Mansureh Soleimani, Ali Reza Ebrahimzadeh Bideskan, Majid Asadi-Shekaari, Hamed Kheradmand, Hossein Haghir
Metabolic Brain Disease December 2012 DOI: 10.1007/s11011-012-9334-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experimental animal study Peer reviewed |
|---|---|
| Sample size | 63 |
| Population | Adult male Sprague-Dawley rats |
| Intervention | MDMA |
| Dose | MDMA 10 and 20 mg/kg; CGS 0.03 mg/kg; SCH 0.03 mg/kg |
| Measures | Morris water maze (MWM), body temperature, electron microscopy, stereological study |
| Topics | MDMA |
| Key findings | MDMA increased body temperature and impaired spatial learning and increased hippocampal dark neurons, especially in CA1. The A2a adenosine antagonist SCH worsened these effects, while the A2a agonist CGS partially protected against the learning deficits and hippocampal cell death, suggesting a potential protective role for A2a receptor stimulation. |
Abstract
There is abundant evidence showing that repeated use of MDMA (3, 4-Methylenedioxymethamphetamine, ecstasy) has been associated with depression, anxiety and deficits in learning and memory, suggesting detrimental effects on hippocampus. Adenosine is an endogenous purine nucleoside that has a neuromodulatory role in the central nervous system. In the present study, we investigated the role of A2a adenosine receptors agonist (CGS) and antagonist (SCH) on the body temperature, learning deficits, and hippocampal cell death induced by MDMA administration. In this study, 63 adult, male, Sprague - Dawley rats were subjected to MDMA (10 and 20 mg/kg) followed by intraperitoneal CGS (0.03 mg/kg) or SCH (0.03 mg/kg) injection. The animals were tested for spatial learning in the Morris water maze (MWM) task performance, accompanied by a recording of body temperature, electron microscopy and stereological study. Our results showed that MDMA treatment increased body temperature significantly, and impaired the ability of rats to locate the hidden platform(P < 0.05). The number of hippocampal dark neurons also increased especially in CA1. These impairments were aggravated by co-administration of A2a antagonist (SCH) with MDMA. Furthermore, the administration of the A2a receptor agonist (CGS) provided partial protection against MWM deficits and hippocampal cell death(P < 0.05). This study provides for the first time evidence that, in contrast to A2a antagonist (SCH) effects, co-administration of A2a agonist (CGS) with MDMA can protect against MDMA hippocampal neurotoxic effects; providing a potential value in the prevention of learning deficits observed in MDMA users. However, the exact mechanism of these interactions requires further studies.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 8
- MDMA Increases Glutamate Release and Reduces Parvalbumin-Positive GABAergic Cells in the Dorsal Hippocampus of the Rat: Role of Cyclooxygenase Journal of Neuroimmune Pharmacology November 17, 2012
- The Role of Adenosine A1 and A2A Receptors in the Caffeine Effect on MDMA-Induced DA and 5-HT Release in the Mouse Striatum Neurotoxicity Research November 13, 2014
- Effects of Stress and MDMA on Hippocampal Gene Expression BioMed Research International 2014
- Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose. Pharmacological Reviews July 1, 2019
- The Mediating Role of A2A Adenosine Receptors in the Mitochondrial Pathway of Apoptotic Hippocampal Cell Death, Following the Administration of MDMA in Rat. Basic and clinical neuroscience 2017
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Cites 11
- Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Journal of Pharmacology and Experimental Therapeutics 1987
- (±3,4-Methylenedioxymethamphetamine Selectively Damages Central Serotonergic Neurons in Nonhuman Primates JAMA July 1, 1988
- The pharmacology of the acute hyperthermic response that follows administration of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) to rats British Journal of Pharmacology 2002
- Exposure to 3,4‐methylenedioxymethamphetamine (MDMA) on postnatal days 11–20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning International Journal of Developmental Neuroscience August 1, 2004
- (+/–)3,4-Methylenedioxymethamphetamine (MDMA) Dose-Dependently Impairs Spatial Learning in the Morris Water Maze after Exposure of Rats to Different Five-Day Intervals from Birth to Postnatal Day Twenty Developmental Neuroscience 2009
and 6 more in the library