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Metabolic phenotype of rats exposed to heroin and potential markers of heroin abuse.

Abstract：

BACKGROUND:Metabolomics allows the high-throughput analysis of low molecular mass compounds in biofluids, which can reflect the metabolic response of the body to heroin exposure and potentially reveal biomarkers of heroin abuse. METHODS:Heroin was administered to Sprague-Dawley rats in increasing doses from 3 to 16.5 mg kg(-1)d(-1) (i.p.) for 10 days, then withdrawn and re-administered for 4 days. The analytes in serum and urine were profiled using gas chromatography-mass spectrometry, and metabolic patterns were evaluated based on the metabolomics data. RESULTS:Both the administration and withdrawal of heroin resulted in aberrant behaviour in the rats; however, the rats gradually became adapted to heroin. Metabolomics data showed that heroin administration caused deviations in the metabolic patterns, whereas heroin withdrawal restored the metabolic patterns towards baseline. Re-administration of heroin caused the metabolic patterns to deviate again. Analysis of the metabolites revealed that heroin induced an acceleration of the tricarboxylic acid cycle and the metabolism of free fatty acids that may contribute to the reduction in observed body weight in the heroin group. Heroin administration decreased tryptophan and 5-hydroxytryptamine levels in peripheral serum but increased urinary tryptophan and 5-hydroxyindoleacetate. Withdrawal of heroin for 4 days efficiently restored all metabolites to baseline, except serum myo-inositol-1-phosphate, threonate, and hydroxyproline in the urine. CONCLUSIONS:Heroin administration significantly perturbed metabolic pathways, elevated energy metabolism, whereas heroin withdrawal restored all but a few metabolites to baseline. These peripheral metabolites were indicated as the surrogates characterising the metabolic effect of heroin on central nervous system function.

journal_name

Drug Alcohol Depend

journal_title

Drug and alcohol dependence

authors

Zheng T,Liu L,Aa J,Wang G,Cao B,Li M,Shi J,Wang X,Zhao C,Gu R,Zhou J,Xiao W,Yu X,Sun R,Zhou Y,Zuo Y,Zhu X

doi

10.1016/j.drugalcdep.2012.06.031

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

177-86

issue

1-3

eissn

0376-8716

issn

1879-0046

pii

S0376-8716(12)00263-3

journal_volume

127

pub_type

杂志文章

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