PMID- 26378923
OWN - NLM
STAT- MEDLINE
DCOM- 20160520
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 9
DP  - 2015
TI  - Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In 
      Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
PG  - e0138431
LID - 10.1371/journal.pone.0138431 [doi]
LID - e0138431
AB  - 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.
FAU - Chiu, Chuang-Hsin
AU  - Chiu CH
AD  - 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.
FAU - Siow, Tiing-Yee
AU  - Siow TY
AD  - Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, 
      Chang Gung University, Kueishan, Taoyuan, Taiwan.
FAU - Weng, Shao-Ju
AU  - Weng SJ
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Hsu, Yi-Hua
AU  - Hsu YH
AD  - Functional and Micro-Magnetic Resonance Imaging Center, Institute of Biomedical 
      Sciences, Academia Sinica, Taipei, Taiwan; Institute of Biomedical Sciences, 
      Academia Sinica, Taipei, Taiwan.
FAU - Huang, Yuahn-Sieh
AU  - Huang YS
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
FAU - Chang, Kang-Wei
AU  - Chang KW
AD  - Institute of Nuclear Energy Research, Taoyaun, Taiwan.
FAU - Cheng, Cheng-Yi
AU  - Cheng CY
AD  - Department of Nuclear Medicine, Tri-Service General Hospital, National Defense 
      Medical Center, Taipei, Taiwan.
FAU - Ma, Kuo-Hsing
AU  - Ma KH
AD  - Department of Biology and Anatomy, National Defense Medical Center, Taipei, 
      Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150917
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 333DO1RDJY (Serotonin)
RN  - 42Z2K6ZL8P (Manganese)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Axons/drug effects/metabolism
MH  - Axotomy/methods
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dorsal Raphe Nucleus/*drug effects
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Manganese/*metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Neurotoxicity Syndromes/metabolism
MH  - Prosencephalon/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/metabolism
MH  - Ventral Tegmental Area/drug effects/metabolism
PMC - PMC4574734
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/09/18 06:00
MHDA- 2016/05/21 06:00
PMCR- 2015/09/17
CRDT- 2015/09/18 06:00
PHST- 2015/01/05 00:00 [received]
PHST- 2015/08/30 00:00 [accepted]
PHST- 2015/09/18 06:00 [entrez]
PHST- 2015/09/18 06:00 [pubmed]
PHST- 2016/05/21 06:00 [medline]
PHST- 2015/09/17 00:00 [pmc-release]
AID - PONE-D-15-00339 [pii]
AID - 10.1371/journal.pone.0138431 [doi]
PST - epublish
SO  - PLoS One. 2015 Sep 17;10(9):e0138431. doi: 10.1371/journal.pone.0138431. 
      eCollection 2015.