Identification of Morphine and Heroin-Treatment in Mice Using Metabonomics

Although heroin and morphine are structural analogues and morphine is a metabolite of heroin, it is not known how the effect of each substance on metabolites in vivo differs. Heroin and morphine were administered to C57BL/6J mice in increasing doses from 2 to 25 and 3 to 9 mg kg(-1) (twice a day, i.p.), respectively, for 20 days. The animals underwent withdrawal for 5 days and were readministered the drugs after 10 days. Serum and urine analytes were profiled using gas chromatography-mass spectrometry (GC-MS), and metabolic patterns were evaluated based on metabonomics data. Metabonomics data showed that heroin administration changed metabolic pattern, and heroin withdrawal did not quickly restore it to baseline levels. A relapse of heroin exposure changed metabolic pattern again. In contrast, although the administration of morphine changed metabolic pattern, whether from morphine withdrawal or relapse, metabolic pattern was similar to control levels. The analysis of metabolites showed that both heroin and morphine interfered with lipid metabolism, the tricarboxylic acid (TCA) cycle and amino acid metabolism. In addition, both heroin and morphine increased the levels of 3-hydroxybutyric acid and citric acid but decreased the serum levels of 2-ketoglutaric acid and tryptophan. Moreover, heroin and morphine reduced the levels of aconitic acid, cysteine, glycine, and oxalic acid in urine. The results show 3-Hydroxybutyric acid, tryptophan, citric acid and 2-ketoglutaric acid can be used as potential markers of opiate abuse in serum, while oxalic acid, aconitic acid, cysteine, and glycine can be used as potential markers in urine.

Automated summary

The study found that heroin and morphine had different effects on metabolic patterns in animals, with heroin not quickly restoring metabolic patterns to baseline levels after withdrawal and causing a change in metabolic pattern upon relapse. Conversely, morphine administration altered metabolic patterns but resulted in similar levels to the control group during withdrawal or relapse. Both heroin and morphine were found to interfere with lipid metabolism, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Heroin and morphine also shared similarities in affecting specific metabolites in serum and urine, showing their potential as markers for opiate abuse.