title: 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was administered to Sprague-Dawley rats in increasing doses from 3 to 16.5 mg kg(-1)d(-1) (i.p.) for 10 days, then withdrawn and re-administered for 4 days.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.
authors: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, No. 24, Tongjia Road, Nanjing 210009, Jiangsu Province, China.
authors: Tian
authors: T
authors: Zheng
authors: Linsheng
authors: L
authors: Liu
authors: Jiye
authors: J
authors: Aa
authors: Guangji
authors: G
authors: Wang
authors: Bei
authors: B
authors: Cao
authors: Mengjie
authors: M
authors: Li
authors: Jian
authors: J
authors: Shi
authors: Xinwen
authors: X
authors: Wang
authors: Chunyan
authors: C
authors: Zhao
authors: Rongrong
authors: R
authors: Gu
authors: Jun
authors: J
authors: Zhou
authors: Wenjing
authors: W
authors: Xiao
authors: Xiaoyi
authors: X
authors: Yu
authors: Runbing
authors: R
authors: Sun
authors: Yahong
authors: Y
authors: Zhou
authors: Yuexian
authors: Y
authors: Zuo
authors: Xuanxuan
authors: X
authors: Zhu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology*; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000175:diagnosis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D055432:Metabolomics / Q000379:methods*; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D003932:Heroin