title: A molecular profile of cocaine abuse includes the differential expression of genes that regulate transcription, chromatin, and dopamine cell phenotype.
abstract: Chronic drug abuse, craving, and relapse are thought to be linked to long-lasting changes in neural gene expression arising through transcriptional and chromatin-related mechanisms. The key contributions of midbrain dopamine (DA)-synthesizing neurons throughout the addiction process provide a compelling rationale for determining the drug-induced molecular changes that occur in these cells. Yet our understanding of these processes remains rudimentary. The postmortem human brain constitutes a unique resource that can be exploited to gain insights into the pathophysiology of complex disorders such as drug addiction. In this study, we analyzed the profiles of midbrain gene expression in chronic cocaine abusers and well-matched drug-free control subjects using microarray and quantitative PCR. A small number of genes exhibited robust differential expression; many of these are involved in the regulation of transcription, chromatin, or DA cell phenotype. Transcript abundances for approximately half of these differentially expressed genes were diagnostic for assigning subjects to the cocaine-abusing vs control cohort. Identification of a molecular signature associated with pathophysiological changes occurring in cocaine abusers' midbrains should contribute to the development of biomarkers and novel therapeutic targets for drug addiction.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Michael J
authors.identifier: 0000000298874309
authors.initials: MJ
authors.lastname: Bannon
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Magen M
authors.initials: MM
authors.lastname: Johnson
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Michelhaugh
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Hartley
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Halter
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: David
authors.affiliation: 1] Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA [2] Center for Molecular Medicine & Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kapatos
authors.affiliation: Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Schmidt
mesh_terms: D001921:Brain / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002908:Chronic Disease; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000378:metabolism*; D046228:Microarray Analysis; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004298:Dopamine