title: Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
abstract: 3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chuang-Hsin
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Chang Gung University, Kueishan, Taoyuan, Taiwan.
authors.forename: Tiing-Yee
authors.initials: TY
authors.lastname: Siow
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Weng
authors.affiliation: Functional and Micro-Magnetic Resonance Imaging Center, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yuahn-Sieh
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Institute of Nuclear Energy Research, Taoyaun, Taiwan.
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Chang
authors.affiliation: Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D019771:Axotomy / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D065847:Dorsal Raphe Nucleus / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008345:Manganese / Q000378:metabolism*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D008345:Manganese; D018817:N-Methyl-3,4-methylenedioxyamphetamine