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EJNMMI Research
Published in: EJNMMI Research 1/2019

Open Access 01-12-2019 | Positron Emission Tomography | Original research

In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine

Authors: Wen-Sheng Huang, Guann-Juh Chen, Tung-Han Tsai, Chen-Yi Cheng, Chyng-Yann Shiue, Kuo-Hsing Ma, Skye Hsin-Hsien Yeh

Published in: EJNMMI Research | Issue 1/2019

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Abstract

Background

Methamphetamine (METH)-associated alterations in the striatal dopamine (DA) system or dopamine transport (DAT) have been identified in clinical and preclinical studies with positron emission tomography (PET) imaging but have not been well correlated with in vivo serotonin transporter (SERT) availability due to the lack of appropriate imaging agents to assess SERTs. N,N-dimethyl-2-(2-amino-4-[18F]-fluorophenylthio) benzylamine (4-[18F]-ADAM) has been developed by our group and validated for its high affinity and selectivity for SERTs, allowing the in vivo examination of SERT density, location, and binding function. The aims of this study were to investigate the potential of SERT imaging using 4-[18F]-ADAM PET to estimate the long-lasting effects of METH-induced serotonergic neurotoxicity, and further determine whether a correlative relationship exists between SERT availability/activity and tyrosine hydroxylase (TH) activity in various brain regions due to the long-lasting consequences of METH treatment.

Results

Male rats received four administrations of METH (5 or 10 mg/kg, s.c.) or saline (1 ml/kg, s.c.) at 1-h intervals. At 30 days post-administration, in vivo SERT availability and activity were measured by 4-[18F]ADAM PET imaging. In contrast to the controls, the uptake of 4-[18F]ADAM in METH-treated mice was significantly reduced in a dose-dependent manner in the midbrain, followed by the hypothalamus, thalamus, striatum, hippocampus, and frontal cortex. The regional effects of METH on TH activity were assessed by quantitative immunohistochemistry and presented as integrated optical density (IOD). A significant decrease in TH immunostaining and IOD ratios was seen in the caudate, putamen, nucleus accumbens, substantia nigra pars compacta, and substantia nigra pars reticulata in the METH-treated rats compared to controls.

Conclusion

The present results suggested that the long-lasting response to METH decreased the uptake of 4-[18F]-ADAM and varied regionally along with TH immunoreactivity. In addition, 4-[18F]ADAM PET could be used to detect serotonergic neuron loss and to evaluate the severity of serotonergic neurotoxicity of METH.
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Metadata
Title
In vivo long-lasting alterations of central serotonin transporter activity and associated dopamine synthesis after acute repeated administration of methamphetamine
Authors
Wen-Sheng Huang
Guann-Juh Chen
Tung-Han Tsai
Chen-Yi Cheng
Chyng-Yann Shiue
Kuo-Hsing Ma
Skye Hsin-Hsien Yeh
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2019
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-019-0557-y

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