Publication Details

Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area.

Authors:McClung CA, Nestler EJ, Zachariou V
Title:Regulation of gene expression by chronic morphine and morphine withdrawal in the locus ceruleus and ventral tegmental area.
Journal:The Journal of neuroscience : the official journal of the Society for Neuroscience Jun 2005 , Vol 25 , pp. 6005-15
Abstract:Morphine dependence is associated with long-term adaptive changes in the brain that involve gene expression. Different behavioral effects of morphine are mediated by different brain regions, for example, the locus ceruleus (LC), a noradrenergic nucleus, is implicated in physical dependence and withdrawal, whereas the ventral tegmental area (VTA), a dopaminergic nucleus, contributes to rewarding and locomotor responses to the drug. However, the global changes in gene expression that occur in these brain regions after morphine exposure and during withdrawal remain unknown. Using DNA microarray analysis in both mice and rats, we now characterize gene expression changes that occur in these brain regions with chronic morphine and antagonist-precipitated withdrawal. In the LC, numerous genes display common regulation between mouse and rat, including tyrosine hydroxylase, prodynorphin, and galanin. Furthermore, we identify clusters of genes that are regulated similarly by chronic morphine and by withdrawal, as well as clusters that show opposite regulation under these two conditions. Interestingly, most gene expression changes that occur in the VTA in response to chronic morphine are different from those seen in the LC, but the gene expression patterns in the two brain regions are very similar after withdrawal. In addition, we examined two genes (prodynorphin and FK506 binding protein 5) that are strongly regulated by chronic morphine or morphine withdrawal in the LC for their role in regulating withdrawal-associated behaviors. Inhibition of either protein profoundly affects withdrawal responses, demonstrating that the genes identified in this study have important functional roles in mediating opiate-induced behaviors.   PUBMED: 15976090
Ontological Annotations:
  • D011506: Proteins (Publication, NCBO Annotator)
  • D001927: Brain Diseases (Publication, NCBO Annotator)
  • D020411: Oligonucleotide Array Sequence Analysis (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D000818: Animals (PubMed MeSH Annotations)
  • D014443: Tyrosine (Publication, NCBO Annotator)
  • D008810: Mice, Inbred C57BL (PubMed MeSH Annotations)
  • D019004: Galanin (Publication, NCBO Annotator)
  • D004364: Pharmaceutical Preparations (Publication, NCBO Annotator)
  • D004247: DNA (Publication, NCBO Annotator)
  • D005786: Gene Expression Regulation (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D001519: Behavior (Publication, NCBO Annotator)
  • D017557: Ventral Tegmental Area (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D000199: Actins (PubMed MeSH Annotations)
  • D002352: Carrier Proteins (Publication, NCBO Annotator)
  • GO:0010468: regulation of gene expression (Publication, NCBO Annotator)
  • D012926: Social Control, Formal (Publication, NCBO Annotator)
  • MA:0000168: brain (Publication, NCBO Annotator)
  • D019970: Cocaine-Related Disorders (Publication, NCBO Annotator)
  • D002467: Cell Nucleus (Publication, NCBO Annotator)
  • D009021: Morphine Dependence (Publication, NCBO Annotator)
  • D008825: Miconazole (Publication, NCBO Annotator)
  • D014446: Tyrosine 3-Monooxygenase (Publication, NCBO Annotator)
  • D008125: Locus Coeruleus (Publication, NCBO Annotator; PubMed MeSH Annotations)
  • D007266: Inhibition (Psychology) (Publication, NCBO Annotator)
  • GO:0005634: nucleus (Publication, NCBO Annotator)
  • D009020: Morphine (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • D046228: Microarray Analysis (Publication, NCBO Annotator)
  • D006899: Mixed Function Oxygenases (Publication, NCBO Annotator)
  • GO:0005528: FK506 binding (Publication, NCBO Annotator)
  • D005987: Glyceraldehyde-3-Phosphate Dehydrogenases (PubMed MeSH Annotations)
  • GO:0005488: binding (Publication, NCBO Annotator)
  • D009293: Opioid-Related Disorders (Publication, NCBO Annotator)
  • D051379: Mice (PubMed MeSH Annotations; Publication, NCBO Annotator)
  • GO:0010467: gene expression (Publication, NCBO Annotator)
  • D051381: Rats (Publication, NCBO Annotator)
  • D006556: Heroin Dependence (Publication, NCBO Annotator)
  • D017008: Negotiating (Publication, NCBO Annotator)
  • D013375: Substance Withdrawal Syndrome (PubMed MeSH Annotations)
  • D016559: Tacrolimus (Publication, NCBO Annotator)
  • D000339: Affect (Publication, NCBO Annotator)
  • D001921: Brain (Publication, NCBO Annotator)
  • D012380: Role (Publication, NCBO Annotator)
  • D022021: Tacrolimus Binding Proteins (Publication, NCBO Annotator)

8 GeneSets from this Publication:


Select gene sets below using the check boxes, and then add them to a project using the pull down below. You can also create a project using the pull down. To view a set, click on the GeneSetID:GeneSet Description shown in green below.
Expand Tier I Mouse DRG 23 Genes provisional GS86421: Table S5: Genes significantly regulated by morphine withdrawal in the mouse VTA [DRG]
Expand Tier I Mouse DRG 14 Genes provisional GS86429: Table S1: Genes significantly regulated by chronic morphine in the mouse LC [DRG]
Expand Tier I Mouse DRG 10 Genes provisional GS86534: Table S1: Genes significantly regulated by chronic morphine in the mouse LC [DRG]
Expand Tier I Mouse DRG 51 Genes provisional GS86762: Table S2: Genes significantly regulated by morphine withdrawal in the mouse LC [DRG]
Expand Tier I Mouse DRG 19 Genes provisional GS86884: Table S2: Genes significantly regulated by morphine withdrawal in the mouse LC [DRG]
Expand Tier I Mouse DRG 14 Genes provisional GS87055: Table S4 (2): Genes significantly regulated by chronic morphine in the mouse VTA [DRG]
Expand Tier I Mouse DRG 15 Genes provisional GS87185: Table S4 (2): Genes significantly regulated by chronic morphine in the mouse VTA [DRG]
Expand Tier I Mouse DRG 43 Genes provisional GS87197: Table S5: Genes significantly regulated by morphine withdrawal in the mouse VTA [DRG]