Single dose of MDMA causes extensive decrement of serotoninergic fibre density without blockage of the fast axonal transport in Dark Agouti rat brain and spinal cord

G. G. Kovács, R. D. Andó, C. Ádori, E. Kirilly, A. Benedek, M. Palkóvits, G. Bagdy

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Prolonged neurotoxicity of the recreational drug, MDMA (3,4- methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporter (5-HTT) immunoreactivity, has been evaluated in the spinal cord and brain areas in Dark Agouti rats, 7 and 180 days after MDMA applications. Immunostaining for amyloid precursor protein (APP) has been performed to examine possible defects of the fast axonal transport, and 5-HTT mRNA expressions were quantified in neurones of medullary raphe nuclei. Seven days after MDMA treatment, a substantial decrease in the density of TpH-immunoreactive fibres was detectable in the frontal cortex, the caudate-putamen, the CA1 region of the hippocampus, and marked decreases were found in the spinal cord. These changes in TpH density showed a high correlation with 5-HTT densities. In contrast, APP-immunoreactive axonal bulbs were not detected in any of the brain regions studied. Seven days after MDMA administrations, significantly elevated 5-HTT mRNA expressions were found in the raphe pallidus and obscurus. Our results suggest that a single dose of MDMA elicits widespread depletion of TpH and 5-HTT immunoreactivity in serotoninergic axons without morphological sign of the blockage of the fast anterograde axonal transport. Our results do not support the notion of MDMA-induced axotomy of serotoninergic neurones. The up-regulation of 5-HTT mRNA expressions 1 week after MDMA injections might indicate the potential recovery of the serotonin system.

Original languageEnglish
Pages (from-to)193-203
Number of pages11
JournalNeuropathology and Applied Neurobiology
Volume33
Issue number2
DOIs
Publication statusPublished - Apr 2007

Fingerprint

N-Methyl-3,4-methylenedioxyamphetamine
Axonal Transport
Spinal Cord
Tryptophan Hydroxylase
Brain
Amyloid beta-Protein Precursor
Messenger RNA
Serotonergic Neurons
Axotomy
Serotonin Plasma Membrane Transport Proteins
Raphe Nuclei
Dasyproctidae
Putamen
Presynaptic Terminals
Street Drugs
Frontal Lobe
Axons
Hippocampus
Serotonin
Up-Regulation

Keywords

  • Axonal transport
  • Ecstasy
  • MDMA
  • Serotonin
  • Serotonin transporter
  • Spinal cord
  • Tryptophan hydroxylase

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

@article{e2a3d57f856b4cfbb53a4382b1b051db,
title = "Single dose of MDMA causes extensive decrement of serotoninergic fibre density without blockage of the fast axonal transport in Dark Agouti rat brain and spinal cord",
abstract = "Prolonged neurotoxicity of the recreational drug, MDMA (3,4- methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporter (5-HTT) immunoreactivity, has been evaluated in the spinal cord and brain areas in Dark Agouti rats, 7 and 180 days after MDMA applications. Immunostaining for amyloid precursor protein (APP) has been performed to examine possible defects of the fast axonal transport, and 5-HTT mRNA expressions were quantified in neurones of medullary raphe nuclei. Seven days after MDMA treatment, a substantial decrease in the density of TpH-immunoreactive fibres was detectable in the frontal cortex, the caudate-putamen, the CA1 region of the hippocampus, and marked decreases were found in the spinal cord. These changes in TpH density showed a high correlation with 5-HTT densities. In contrast, APP-immunoreactive axonal bulbs were not detected in any of the brain regions studied. Seven days after MDMA administrations, significantly elevated 5-HTT mRNA expressions were found in the raphe pallidus and obscurus. Our results suggest that a single dose of MDMA elicits widespread depletion of TpH and 5-HTT immunoreactivity in serotoninergic axons without morphological sign of the blockage of the fast anterograde axonal transport. Our results do not support the notion of MDMA-induced axotomy of serotoninergic neurones. The up-regulation of 5-HTT mRNA expressions 1 week after MDMA injections might indicate the potential recovery of the serotonin system.",
keywords = "Axonal transport, Ecstasy, MDMA, Serotonin, Serotonin transporter, Spinal cord, Tryptophan hydroxylase",
author = "Kov{\'a}cs, {G. G.} and And{\'o}, {R. D.} and C. {\'A}dori and E. Kirilly and A. Benedek and M. Palk{\'o}vits and G. Bagdy",
year = "2007",
month = "4",
doi = "10.1111/j.1365-2990.2006.00790.x",
language = "English",
volume = "33",
pages = "193--203",
journal = "Neuropathology and Applied Neurobiology",
issn = "0305-1846",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Single dose of MDMA causes extensive decrement of serotoninergic fibre density without blockage of the fast axonal transport in Dark Agouti rat brain and spinal cord

AU - Kovács, G. G.

AU - Andó, R. D.

AU - Ádori, C.

AU - Kirilly, E.

AU - Benedek, A.

AU - Palkóvits, M.

AU - Bagdy, G.

PY - 2007/4

Y1 - 2007/4

N2 - Prolonged neurotoxicity of the recreational drug, MDMA (3,4- methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporter (5-HTT) immunoreactivity, has been evaluated in the spinal cord and brain areas in Dark Agouti rats, 7 and 180 days after MDMA applications. Immunostaining for amyloid precursor protein (APP) has been performed to examine possible defects of the fast axonal transport, and 5-HTT mRNA expressions were quantified in neurones of medullary raphe nuclei. Seven days after MDMA treatment, a substantial decrease in the density of TpH-immunoreactive fibres was detectable in the frontal cortex, the caudate-putamen, the CA1 region of the hippocampus, and marked decreases were found in the spinal cord. These changes in TpH density showed a high correlation with 5-HTT densities. In contrast, APP-immunoreactive axonal bulbs were not detected in any of the brain regions studied. Seven days after MDMA administrations, significantly elevated 5-HTT mRNA expressions were found in the raphe pallidus and obscurus. Our results suggest that a single dose of MDMA elicits widespread depletion of TpH and 5-HTT immunoreactivity in serotoninergic axons without morphological sign of the blockage of the fast anterograde axonal transport. Our results do not support the notion of MDMA-induced axotomy of serotoninergic neurones. The up-regulation of 5-HTT mRNA expressions 1 week after MDMA injections might indicate the potential recovery of the serotonin system.

AB - Prolonged neurotoxicity of the recreational drug, MDMA (3,4- methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporter (5-HTT) immunoreactivity, has been evaluated in the spinal cord and brain areas in Dark Agouti rats, 7 and 180 days after MDMA applications. Immunostaining for amyloid precursor protein (APP) has been performed to examine possible defects of the fast axonal transport, and 5-HTT mRNA expressions were quantified in neurones of medullary raphe nuclei. Seven days after MDMA treatment, a substantial decrease in the density of TpH-immunoreactive fibres was detectable in the frontal cortex, the caudate-putamen, the CA1 region of the hippocampus, and marked decreases were found in the spinal cord. These changes in TpH density showed a high correlation with 5-HTT densities. In contrast, APP-immunoreactive axonal bulbs were not detected in any of the brain regions studied. Seven days after MDMA administrations, significantly elevated 5-HTT mRNA expressions were found in the raphe pallidus and obscurus. Our results suggest that a single dose of MDMA elicits widespread depletion of TpH and 5-HTT immunoreactivity in serotoninergic axons without morphological sign of the blockage of the fast anterograde axonal transport. Our results do not support the notion of MDMA-induced axotomy of serotoninergic neurones. The up-regulation of 5-HTT mRNA expressions 1 week after MDMA injections might indicate the potential recovery of the serotonin system.

KW - Axonal transport

KW - Ecstasy

KW - MDMA

KW - Serotonin

KW - Serotonin transporter

KW - Spinal cord

KW - Tryptophan hydroxylase

UR - http://www.scopus.com/inward/record.url?scp=33847694981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847694981&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2990.2006.00790.x

DO - 10.1111/j.1365-2990.2006.00790.x

M3 - Article

C2 - 17359360

AN - SCOPUS:33847694981

VL - 33

SP - 193

EP - 203

JO - Neuropathology and Applied Neurobiology

JF - Neuropathology and Applied Neurobiology

SN - 0305-1846

IS - 2

ER -