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

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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.

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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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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA

    Ashwin A. Patkar, Steve Rozen, Paolo Mannelli, Chi-Un Pae, K. Ranga Krishnan & Rima Kaddurah-Daouk

  2. Department of Systems Biochemistry, Bedford VA Medical Center, Bedford, MA, USA

    Wayne Matson

  3. Duke-NUS Graduate Medical School, Singapore, Singapore

    Steve Rozen & K. Ranga Krishnan

  4. The Catholic University of Korea College of Medicine, Seoul, Republic of Korea

    Chi-Un Pae

  5. Duke University Medical Center, 2218 Elder Street, Suite 127, Durham, NC, 27705, USA

    Ashwin A. Patkar

  6. Duke University Medical Center, Rm. 3552 Blue Zone, Duke South/Clinics, Box 3903, Durham, NC, 27710, USA

    Rima Kaddurah-Daouk

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  1. Ashwin A. Patkar
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  2. Steve Rozen
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  4. Wayne Matson
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  6. K. Ranga Krishnan
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  7. Rima Kaddurah-Daouk
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Corresponding authors

Correspondence to Ashwin A. Patkar or Rima Kaddurah-Daouk.

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Patkar, A.A., Rozen, S., Mannelli, P. et al. Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study. Psychopharmacology 206, 479–489 (2009). https://doi.org/10.1007/s00213-009-1625-1

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  • DOI: https://doi.org/10.1007/s00213-009-1625-1

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