(±)3,4-methylenedioxymethamphetamine (“ecstasy”) treatment modulates expression of neurotrophins and their receptors in multiple regions of adult rat brain

Authors

  • Ann M. Hemmerle,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
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  • Jonathan W. Dickerson,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
    Current affiliation:
    1. Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232
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  • Nicole R. Herring,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Division of Neurology, Department of Pediatrics, University of Cincinnati and Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229
    Current affiliation:
    1. Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202
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  • Tori L. Schaefer,

    1. Division of Neurology, Department of Pediatrics, University of Cincinnati and Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229
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  • Charles V. Vorhees,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Division of Neurology, Department of Pediatrics, University of Cincinnati and Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229
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  • Michael T. Williams,

    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Division of Neurology, Department of Pediatrics, University of Cincinnati and Cincinnati Children's Research Foundation, Cincinnati, Ohio 45229
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  • Kim B. Seroogy

    Corresponding author
    1. Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio 45267
    2. Department of Neurology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267
    • Department of Neurology, The Selma Schottenstein Harris Laboratory for Research in Parkinson's, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Medical Sciences Building, ML 0536, 231 Albert Sabin Way, Cincinnati, OH 45267
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Abstract

(±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment. J. Comp. Neurol. 520:2459–2474, 2012. © 2012 Wiley Periodicals, Inc.

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