Transcriptional Profiling in the Human Prefrontal Cortex: Evidence for Two Activational States Associated with Cocaine Abuse

Overview

Journal Pharmacogenomics J

Specialties Genetics
Molecular Biology
Pharmacology

Date 2003 Mar 12

PMID 12629581

Citations 39

Authors

E Lehrmann

J Oyler

M P Vawter

T M Hyde

B Kolachana

J E Kleinman

M A Huestis

K G Becker

W J Freed

Affiliations

Soon will be listed here.

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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References

McFarland K, Kalivas P . The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci. 2001; 21(21):8655-63. PMC: 6762812. View

Freeman W, Brebner K, Lynch W, Robertson D, Roberts D, Vrana K . Cocaine-responsive gene expression changes in rat hippocampus. Neuroscience. 2001; 108(3):371-80. DOI: 10.1016/s0306-4522(01)00432-8. View

Young M, Nair R, Bucheimer N, Tulsian P, Brown N, Chapp C . Transactivation of Fra-1 and consequent activation of AP-1 occur extracellular signal-regulated kinase dependently. Mol Cell Biol. 2002; 22(2):587-98. PMC: 139745. DOI: 10.1128/MCB.22.2.587-598.2002. View

Lee P, Sladek R, Greenwood C, Hudson T . Control genes and variability: absence of ubiquitous reference transcripts in diverse mammalian expression studies. Genome Res. 2002; 12(2):292-7. PMC: 155273. DOI: 10.1101/gr.217802. View

Barrett T, Cheadle C, Wood W, Teichberg D, Donovan D, Freed W . Assembly and use of a broadly applicable neural cDNA microarray. Restor Neurol Neurosci. 2002; 18(2-3):127-35. View

Romanczyk T, Weickert C, Webster M, Herman M, Akil M, Kleinman J . Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan. Eur J Neurosci. 2002; 15(2):269-80. DOI: 10.1046/j.0953-816x.2001.01858.x. View

Bonson K, Grant S, Contoreggi C, Links J, Metcalfe J, Weyl H . Neural systems and cue-induced cocaine craving. Neuropsychopharmacology. 2002; 26(3):376-86. DOI: 10.1016/S0893-133X(01)00371-2. View

Middleton F, Mirnics K, Pierri J, Lewis D, Levitt P . Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J Neurosci. 2002; 22(7):2718-29. PMC: 6758309. DOI: 20026209. View

Mash D, Pablo J, Ouyang Q, Hearn W, Izenwasser S . Dopamine transport function is elevated in cocaine users. J Neurochem. 2002; 81(2):292-300. DOI: 10.1046/j.1471-4159.2002.00820.x. View

10.

Mayfield R, Lewohl J, Dodd P, Herlihy A, Liu J, Harris R . Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics. J Neurochem. 2002; 81(4):802-13. DOI: 10.1046/j.1471-4159.2002.00860.x. View

11.

Ikeda M, Dohi T, Tsujimoto A . Inhibition of gamma-aminobutyric acid release from synaptosomes by local anesthetics. Anesthesiology. 1983; 58(6):495-9. DOI: 10.1097/00000542-198306000-00002. View

12.

Strittmatter S, Valenzuela D, Kennedy T, Neer E, Fishman M . G0 is a major growth cone protein subject to regulation by GAP-43. Nature. 1990; 344(6269):836-41. DOI: 10.1038/344836a0. View

13.

Nestler E, Terwilliger R, Walker J, Sevarino K, Duman R . Chronic cocaine treatment decreases levels of the G protein subunits Gi alpha and Go alpha in discrete regions of rat brain. J Neurochem. 1990; 55(3):1079-82. DOI: 10.1111/j.1471-4159.1990.tb04602.x. View

14.

Strittmatter S, Valenzuela D, Sudo Y, Linder M, Fishman M . An intracellular guanine nucleotide release protein for G0. GAP-43 stimulates isolated alpha subunits by a novel mechanism. J Biol Chem. 1991; 266(33):22465-71. View

15.

Guitart X, Nestler E . Neurofilament proteins and the mesolimbic dopamine system: common regulation by chronic morphine and chronic cocaine in the rat ventral tegmental area. J Neurosci. 1992; 12(6):2165-76. PMC: 6575935. View

16.

Striplin C, Kalivas P . Correlation between behavioral sensitization to cocaine and G protein ADP-ribosylation in the ventral tegmental area. Brain Res. 1992; 579(2):181-6. DOI: 10.1016/0006-8993(92)90049-f. View

17.

Vandenbergh D, Persico A, Hawkins A, Griffin C, Li X, Jabs E . Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics. 1992; 14(4):1104-6. DOI: 10.1016/s0888-7543(05)80138-7. View

18.

Guitart X, Marby D, Kosten T, Nestler E . Fischer and Lewis rat strains differ in basal levels of neurofilament proteins and their regulation by chronic morphine in the mesolimbic dopamine system. Synapse. 1992; 12(3):242-53. DOI: 10.1002/syn.890120310. View

19.

Kalivas P, Duffy P . Time course of extracellular dopamine and behavioral sensitization to cocaine. II. Dopamine perikarya. J Neurosci. 1993; 13(1):276-84. PMC: 6576314. View

20.

Barton A, Pearson R, Najlerahim A, Harrison P . Pre- and postmortem influences on brain RNA. J Neurochem. 1993; 61(1):1-11. DOI: 10.1111/j.1471-4159.1993.tb03532.x. View