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The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study

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.

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Acknowledgment

The data used in this paper was extracted from PhD thesis of F. Kermanian. This project was supported financially by the Vice Chancellor for Research, Mashhad University of Medical Sciences; Mashhad, Iran (Grant No. 89451). The authors would like to thank the staffs of the Cellular and Molecular Research Center, Tehran University of Medical Sciences, Tehran, Iran.

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Correspondence to Hossein Haghir.

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Kermanian, F., Mehdizadeh, M., Soleimani, M. et al. The role of adenosine receptor agonist and antagonist on Hippocampal MDMA detrimental effects; a structural and behavioral study. Metab Brain Dis 27, 459–469 (2012). https://doi.org/10.1007/s11011-012-9334-6

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Keywords

  • 3, 4-methylenedioxymethamphetamine
  • Adenosine receptors
  • Morris water maze
  • Cell death