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Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse

The Pharmacogenomics Journal volume 3, pages 27–40 (2003)Cite this article

ABSTRACT

CNS-focused cDNA microarrays were used to examine gene expression profiles in dorsolateral prefrontal cortex (dlPFC, Area 46) from seven individual sets of age- and post-mortem interval-matched male cocaine abusers and controls. The presence of cocaine and related metabolites was confirmed by gas chromatography-mass spectrometry. Sixty-five transcripts were differentially expressed, indicating alterations in energy metabolism, mitochondria and oligodendrocyte function, cytoskeleton and related signaling, and neuronal plasticity. There was evidence for two distinct states of transcriptional regulation, with increases in gene expression predominating in subjects testing positive for a metabolite indicative of recent ‘crack’ cocaine abuse and decreased expression profiles in the remaining cocaine subjects. This pattern was confirmed by quantitative polymerase chain reaction for select transcripts. These data suggest that cocaine abuse targets a distinct subset of genes in the dlPFC, resulting in either a state of acute activation in which increased gene expression predominates, or a relatively destimulated, refractory phase.

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Abbreviations

PFC:

prefrontal cortex

DlPFC:

dorsolateral prefrontal cortex

CDNA:

complementary DNA

DNA:

deoxyribonucleic acid

RNA:

ribonucleic acid

PCR:

polymerase chain reaction

QPCR:

quantitative polymerase chain reaction

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Acknowledgements

The authors gratefully acknowledge the expert assistance of Diane Teichberg and Chris Cheadle (DNA Array Unit, NIA IRP), and by Aaron Russell (BIS, NIDA IRP).

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Authors and Affiliations

  1. Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA

    E Lehrmann, M P Vawter & W J Freed

  2. Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA

    J Oyler & M A Huestis

  3. University of California, Irvine, Psychiatry & Human Behavior, Irvine, CA, USA

    M P Vawter

  4. Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, DHHS, Bethesda, MD, USA

    T M Hyde, B Kolachana & J E Kleinman

  5. DNA Array Unit, Research Resources Branch, National Institute on Aging, NIH, DHHS, Baltimore, MD, USA

    K G Becker

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Lehrmann, E., Oyler, J., Vawter, M. et al. Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse. Pharmacogenomics J 3, 27–40 (2003). https://doi.org/10.1038/sj.tpj.6500146

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