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

Chiu CH, Siow TY, Weng SJ, Hsu YH, Huang YS, Chang KW, Cheng CY, Ma KH - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Anatomical interrelationships of the assessed regions.(A) Sagittal view of the midbrain raphe nucleus (RN) and its downstream VTA/IP, MFB, and striatum. (B) Mn2+ injection site on the rat brain atlas and on MEMRI images.
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pone.0138431.g002: Anatomical interrelationships of the assessed regions.(A) Sagittal view of the midbrain raphe nucleus (RN) and its downstream VTA/IP, MFB, and striatum. (B) Mn2+ injection site on the rat brain atlas and on MEMRI images.

Mentions: After image acquisition, data were analyzed using MRVision software version 1.6.6 (MRVision, Winchester, MA, USA). The T1WIs of each region of interest (ROI) were defined as a series. The T1WIs of each series were manually realigned to the same orientation before processing. ROI placement was performed by two experienced imaging analysts who were blind to the states of the rats under investigation. ROIs were drawn for the VTA, MFB, and striatum based on the Mn2+-enhanced T1WIs at different time points, because the period of optimal signal enhancement differed between different regions. The ROIs were manually drawn according to the rat stereotactic atlas as well as the spatial extent of signal enhancement. The VTA and MFB were defined based on the sagittal- and coronal-view T1WIs obtained 8 h post-Mn2+ infusion, and the same ROI was then retrospectively applied to all images over all three time intervals. At 38 h after the Mn2+ infusion, the striatum was defined based on the axial-view T1WIs obtained 38 h after the Mn2+ infusion. The ROI of the striatum was drawn on the slice showed the largest cross section of the structure. Fig 2 illustrates the anatomical positions of the assessed regions: the VTA/interpeduncular nucleus (IP) and the DRN mainly projecting to the striatum via the MFB. Owing to the limitations of MEMRI, the VTA and the IP were structurally indistinguishable and treated as one region for data processing purposes.


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

Chiu CH, Siow TY, Weng SJ, Hsu YH, Huang YS, Chang KW, Cheng CY, Ma KH - PLoS ONE (2015)

Anatomical interrelationships of the assessed regions.(A) Sagittal view of the midbrain raphe nucleus (RN) and its downstream VTA/IP, MFB, and striatum. (B) Mn2+ injection site on the rat brain atlas and on MEMRI images.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4574734&req=5

pone.0138431.g002: Anatomical interrelationships of the assessed regions.(A) Sagittal view of the midbrain raphe nucleus (RN) and its downstream VTA/IP, MFB, and striatum. (B) Mn2+ injection site on the rat brain atlas and on MEMRI images.
Mentions: After image acquisition, data were analyzed using MRVision software version 1.6.6 (MRVision, Winchester, MA, USA). The T1WIs of each region of interest (ROI) were defined as a series. The T1WIs of each series were manually realigned to the same orientation before processing. ROI placement was performed by two experienced imaging analysts who were blind to the states of the rats under investigation. ROIs were drawn for the VTA, MFB, and striatum based on the Mn2+-enhanced T1WIs at different time points, because the period of optimal signal enhancement differed between different regions. The ROIs were manually drawn according to the rat stereotactic atlas as well as the spatial extent of signal enhancement. The VTA and MFB were defined based on the sagittal- and coronal-view T1WIs obtained 8 h post-Mn2+ infusion, and the same ROI was then retrospectively applied to all images over all three time intervals. At 38 h after the Mn2+ infusion, the striatum was defined based on the axial-view T1WIs obtained 38 h after the Mn2+ infusion. The ROI of the striatum was drawn on the slice showed the largest cross section of the structure. Fig 2 illustrates the anatomical positions of the assessed regions: the VTA/interpeduncular nucleus (IP) and the DRN mainly projecting to the striatum via the MFB. Owing to the limitations of MEMRI, the VTA and the IP were structurally indistinguishable and treated as one region for data processing purposes.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus