Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.

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...

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Main Authors: Chuang-Hsin Chiu, Tiing-Yee Siow, Shao-Ju Weng, Yi-Hua Hsu, Yuahn-Sieh Huang, Kang-Wei Chang, Cheng-Yi Cheng, Kuo-Hsing Ma
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4574734?pdf=render
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author Chuang-Hsin Chiu
Tiing-Yee Siow
Shao-Ju Weng
Yi-Hua Hsu
Yuahn-Sieh Huang
Kang-Wei Chang
Cheng-Yi Cheng
Kuo-Hsing Ma
author_facet Chuang-Hsin Chiu
Tiing-Yee Siow
Shao-Ju Weng
Yi-Hua Hsu
Yuahn-Sieh Huang
Kang-Wei Chang
Cheng-Yi Cheng
Kuo-Hsing Ma
author_sort Chuang-Hsin Chiu
collection DOAJ
description 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.
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spelling doaj.art-2ef17ffb40314374a4c06a9ac4cfc96e2022-12-22T02:39:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013843110.1371/journal.pone.0138431Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.Chuang-Hsin ChiuTiing-Yee SiowShao-Ju WengYi-Hua HsuYuahn-Sieh HuangKang-Wei ChangCheng-Yi ChengKuo-Hsing Ma3,4-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.http://europepmc.org/articles/PMC4574734?pdf=render
spellingShingle Chuang-Hsin Chiu
Tiing-Yee Siow
Shao-Ju Weng
Yi-Hua Hsu
Yuahn-Sieh Huang
Kang-Wei Chang
Cheng-Yi Cheng
Kuo-Hsing Ma
Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
PLoS ONE
title Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
title_full Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
title_fullStr Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
title_full_unstemmed Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
title_short Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study.
title_sort effect of mdma induced axotomy on the dorsal raphe forebrain tract in rats an in vivo manganese enhanced magnetic resonance imaging study
url http://europepmc.org/articles/PMC4574734?pdf=render
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