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Psychopharmacology

, Volume 206, Issue 3, pp 479–489 | Cite as

Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study

  • Ashwin A. Patkar
  • Steve Rozen
  • Paolo Mannelli
  • Wayne Matson
  • Chi-Un Pae
  • K. Ranga Krishnan
  • Rima Kaddurah-Daouk
Original Investigation

Abstract

Background

Mapping metabolic “signatures” can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets.

Objective

We examined the differences in metabolites related to the tyrosine, tryptophan, purine, and oxidative stress pathways between cocaine-dependent subjects and healthy controls. Several of these metabolites serve as biological indices underlying the mechanisms of reinforcement, toxicity, and oxidative stress.

Methods

Metabolomic analysis was performed in 18 DSM-IV-diagnosed cocaine-dependent individuals with at least 2 weeks of abstinence and ten drug-free controls. Plasma concentrations of 37 known metabolites were analyzed and compared using a liquid chromatography electrochemical array platform. Multivariate analyses were used to study the relationship between severity of drug use [Addiction Severity Index (ASI) scores] and biological measures.

Results

Cocaine subjects showed significantly higher levels of n-methylserotonin (p < 0.0017) and guanine (p < 0.0031) and lower concentrations of hypoxanthine (p < 0.0002), anthranilate (p < 0.0024), and xanthine (p < 0.012), compared to controls. Multivariate analyses showed that a combination of n-methylserotonin and xanthine contributed to 73% of the variance in predicting the ASI scores (p < 0.0001). Logistic regression showed that a model combining n-methylserotonin, xanthine, xanthosine, and guanine differentiated cocaine and control groups with no overlap.

Conclusions

Alterations in the methylation processes in the serotonin pathways and purine metabolism seem to be associated with chronic exposure to cocaine. Given the preliminary nature and cross-sectional design of the study, the findings need to be confirmed in larger samples of cocaine-dependent subjects, preferably in a longitudinal design.

Keywords

Metabolomics Methylation n methyl serotonin Cocaine Tryptophan Addiction Purine 

Notes

Acknowledgments

This research was supported in part by grants DA00340 and DA015504 to AAP from the National Institute on Drug Abuse and also with funding from National Institutes of Health grants R24 GM078233, “The Metabolomics Research Network” (R.K.-D.), SMRI (R.K.-D.), NARSAD (R.K.-D.), and R01 NS054008-01A2, (R.K.-D.).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Ashwin A. Patkar
    • 1
    • 5
  • Steve Rozen
    • 1
    • 3
  • Paolo Mannelli
    • 1
  • Wayne Matson
    • 2
  • Chi-Un Pae
    • 1
    • 4
  • K. Ranga Krishnan
    • 1
    • 3
  • Rima Kaddurah-Daouk
    • 1
    • 6
  1. 1.Department of Psychiatry and Behavioral SciencesDuke University Medical CenterDurhamUSA
  2. 2.Department of Systems BiochemistryBedford VA Medical CenterBedfordUSA
  3. 3.Duke-NUS Graduate Medical SchoolSingaporeSingapore
  4. 4.The Catholic University of Korea College of MedicineSeoulRepublic of Korea
  5. 5.Duke University Medical CenterDurhamUSA
  6. 6.Duke University Medical CenterDurhamUSA

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