Abstract
Chronic cocaine use elicits changes in the pattern of gene expression within reinforcement-related, dopaminergic regions. cDNA hybridization arrays were used to illuminate cocaine-regulated genes in the nucleus accumbens (NAcc) of non-human primates (Macaca fascicularis; cynomolgus macaque), treated daily with escalating doses of cocaine over one year. Changes seen in mRNA levels by hybridization array analysis were confirmed at the level of protein (via specific immunoblots). Significantly up-regulated genes included: protein kinase A alpha catalytic subunit (PKA(calpha)); cell adhesion tyrosine kinase beta (PYK2); mitogen activated protein kinase kinase 1 (MEK1); and beta-catenin. While some of these changes exist in previously described cocaine-responsive models, others are novel to any model of cocaine use. All of these adaptive responses coexist within a signaling scheme that could account for known inductions of genes(e.g. fos and jun proteins, and cyclic AMP response element binding protein) previously shown to be relevant to cocaine's behavioral actions. The complete data set from this experiment has been posted to the newly created Drug and Alcohol Abuse Array Data Consortium (http://www.arraydata.org) for mining by the general research community.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CCAAT-Enhancer-Binding Proteins / biosynthesis
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CCAAT-Enhancer-Binding Proteins / genetics
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Clusterin
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Cocaine / pharmacology*
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Cocaine / toxicity
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Cocaine-Related Disorders / genetics*
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Cocaine-Related Disorders / metabolism
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Cyclic AMP-Dependent Protein Kinases / biosynthesis
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Cyclic AMP-Dependent Protein Kinases / genetics
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Cytoskeletal Proteins / biosynthesis
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Cytoskeletal Proteins / genetics
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Focal Adhesion Kinase 2
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Gene Expression Regulation / drug effects*
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Glycoproteins / biosynthesis
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Glycoproteins / genetics
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Janus Kinase 1
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MAP Kinase Kinase 1
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Macaca fascicularis
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Male
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Mitogen-Activated Protein Kinase Kinases / biosynthesis
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Mitogen-Activated Protein Kinase Kinases / genetics
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Molecular Chaperones / biosynthesis
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Molecular Chaperones / genetics
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NFI Transcription Factors
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / genetics
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Nucleus Accumbens / drug effects*
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Nucleus Accumbens / metabolism
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Oligonucleotide Array Sequence Analysis
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Protein Serine-Threonine Kinases / biosynthesis
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Protein Serine-Threonine Kinases / genetics
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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / genetics
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RNA, Messenger / biosynthesis
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Reinforcement, Psychology
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Sensitivity and Specificity
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Trans-Activators*
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Transcription Factor CHOP
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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beta Catenin
Substances
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CCAAT-Enhancer-Binding Proteins
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Clusterin
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Cytoskeletal Proteins
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Glycoproteins
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Molecular Chaperones
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NFI Transcription Factors
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Nerve Tissue Proteins
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RNA, Messenger
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Trans-Activators
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Transcription Factors
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beta Catenin
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Transcription Factor CHOP
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 2
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JAK1 protein, human
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Janus Kinase 1
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Protein Serine-Threonine Kinases
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Cyclic AMP-Dependent Protein Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases
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Cocaine