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Activation of 5-HT3 receptors leads to altered responses 6 months after MDMA treatment

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

The recreational drug “Ecstasy” [3,4-methylenedioxymethamphetamine (MDMA)] has a well-characterised neurotoxic effect on the 5-hydroxytryptamine (5-HT) neurons in animals. Despite intensive studies, the long-term functional consequencies of the 5-HT neurodegeneration remains elusive. The aim of this study was to investigate whether any alteration of 5-hydroxytryptamine-3 (5-HT3) receptor functions on the sleep–wake cycle, motor activity, and quantitative EEG could be detected 6 months after a single dose of 15 mg/kg of MDMA. The selective 5-HT3 receptor agonist m-chlorophenylbiguanide (mCPBG; 1 mg/kg, i.p.) or vehicle was administered to freely moving rats pre-treated with MDMA (15 mg/kg, i.p.) or vehicle 6 months earlier. Polysomnographic and motor activity recordings were performed. Active wake (AW), passive wake (PW), light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2), and paradoxical sleep were classified. In addition, EEG power spectra were calculated for the second hour after mCPBG treatment for each stage. AW increased and SWS-1 decreased in the second hour after mCPBG treatment in control animals. mCPBG caused significant changes in the EEG power in states with cortical activation (AW, PW, paradoxical sleep). In addition, mCPBG had a biphasic effect on hippocampal theta power in AW with a decrease in 7 Hz and a stage-selective increase in the upper range (8–9 Hz). Effects of mCPBG on the time spent in AW and SWS-1 were eliminated or reduced in MDMA-treated animals. In addition, mCPBG did not increase the upper theta power of AW in rats pre-treated with MDMA. These data suggest long-term changes in 5-HT3 receptor function after MDMA.

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Acknowledgments

This study was supported by the Sixth Framework Programme of the E.C., LSHM-CT-2004-503474, the Hungarian Research Fund Grant T020500 and M27976, the Ministry of Health Research Grant 460/2006, the Fund Management of Ministry of Education OMFB 01926/2002, PhD Fellowship Program of the Semmelweis University, Ministry of Education, Hungary, and the Hungarian National Scientific Research Fund (OTKA, K 68960).

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Authors and Affiliations

  1. Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4, 1089, Budapest, Hungary

    Norbert Gyongyosi, Brigitta Balogh, Zita Katai, Eszter Molnar, Rudolf Laufer, Kornelia Tekes & Gyorgy Bagdy

  2. Department of Physiology, Semmelweis University, IX. Tüzoltó utca 37-47, 1094, Budapest, Hungary

    Norbert Gyongyosi

  3. Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary

    Gyorgy Bagdy

  4. Group of Neurochemistry, Hungarian Academy of Science, Semmelweis University, Budapest, Hungary

    Gyorgy Bagdy

  5. Group of Neuropsychopharmacology, Hungarian Academy of Science, Semmelweis University, Budapest, Hungary

    Gyorgy Bagdy

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  1. Norbert Gyongyosi
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Correspondence to Gyorgy Bagdy.

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Gyongyosi, N., Balogh, B., Katai, Z. et al. Activation of 5-HT3 receptors leads to altered responses 6 months after MDMA treatment. J Neural Transm 117, 285–292 (2010). https://doi.org/10.1007/s00702-009-0357-z

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  • DOI: https://doi.org/10.1007/s00702-009-0357-z

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