Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse.
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.
Lehrmann
E
E
Cellular Neurobiology Research Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, MD 21224, USA. elehrman@intra.nida.nih.gov
Oyler
J
J
Vawter
M P
MP
Hyde
T M
TM
Kolachana
B
B
Kleinman
J E
JE
Huestis
M A
MA
Becker
K G
KG
Freed
W J
WJ
D000328:Adult; D016000:Cluster Analysis; D019970:Cocaine-Related Disorders / Q000235:genetics*; D016578:Crack Cocaine / Q000009:adverse effects; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction / Q000379:methods; D017397:Prefrontal Cortex / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*
D016578:Crack Cocaine