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.
authors.affiliation: Department of Neuropathology, National Institute of Psychiatry and Neurology, Budapest, Hungary.
authors.forename: G G
authors.initials: GG
authors.lastname: Kovács
authors.forename: R D
authors.initials: RD
authors.lastname: Andó
authors.forename: C
authors.initials: C
authors.lastname: Adori
authors.forename: E
authors.initials: E
authors.lastname: Kirilly
authors.forename: A
authors.initials: A
authors.lastname: Benedek
authors.forename: M
authors.initials: M
authors.lastname: Palkovits
authors.forename: G
authors.initials: G
authors.lastname: Bagdy
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009412:Nerve Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine