1. ¹Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA
2. ²Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD, USA
3. ³University of California, Irvine, Psychiatry & Human Behavior, Irvine, CA, USA
4. ⁴Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, DHHS, Bethesda, MD, USA
5. ⁵DNA Array Unit, Research Resources Branch, National Institute on Aging, NIH, DHHS, Baltimore, MD, USA

Correspondence: E Lehrmann, NIDA-IRP, NIH, DHHS 5500 Nathan Shock Drive, Baltimore MD 21224, USA. E-mail: elehrman@intra.nida.nih.gov; Tel: +1 410 550 6565 Ext. 136; Fax: +1 410 550 1621

Received 4 October 2002; Accepted 8 October 2002.

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.