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PMID: 1825356 Published · ppublish English Journal Article

Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 4 ·1991-02-15 ·Pages 1291-5

Young ST, Porrino LJ, Iadarola MJ

Abstract

The protooncogene c-fos produces a phosphoprotein, Fos, which regulates gene transcription processes. In neuronal systems, Fos has been proposed to couple synaptic transmission to changes in gene expression by acting in the cell nucleus in concert with other proteins to form complexes in the promoter regions of target genes. We report here that the acute administration of a single dose of the indirect-acting dopaminergic agonist cocaine increases multiple Fos proteins in rat caudate nucleus. The increase is dose-dependent and is apparent immunocytochemically at 1 hr, maximal at 2 hr, and absent 48 hr after treatment. The increase seen immunocytochemically is composed of several molecular weight species as assessed by Western blotting of proteins from isolated striatal cell nuclei. Administration of the specific dopaminergic receptor antagonists sulpiride and SCH-23390 prior to cocaine support a significant role for D1 but not for D2 receptors in mediating this effect. These data indicate that D1 dopamine receptors are linked to a cellular immediate-early gene system(s) and suggest an action of cocaine at one or more levels of gene expression via modulation of transcriptional processes in activated cells.

Related Genes
c-fos
MeSH Terms
Amino Acid Sequence Animals Antibodies Benzazepines/pharmacology Blotting, Western Brain/drug effects,metabolism Caudate Nucleus/metabolism Cell Nucleus/drug effects,metabolism Cocaine/pharmacology Corpus Striatum/metabolism Enzyme Induction Kinetics Male Molecular Sequence Data Molecular Weight Peptides/chemical synthesis Protein-Tyrosine Kinases/biosynthesis Proto-Oncogene Proteins/biosynthesis Proto-Oncogene Proteins c-fos Putamen/metabolism Rats Rats, Inbred Strains Receptors, Dopamine/drug effects,physiology Receptors, Dopamine D1 Reference Values Sulpiride/pharmacology
Chemicals
Antibodies Benzazepines Peptides Proto-Oncogene Proteins Proto-Oncogene Proteins c-fos Receptors, Dopamine Receptors, Dopamine D1 Sulpiride Protein-Tyrosine Kinases Cocaine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Young S T
Laboratory of Cerebral Metabolism, National Institutes of Mental Health, National Institutes of Health, Bethesda, MD 20892.
Porrino L J
Iadarola M J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.4.1291
Published
1991-02-15
Pages
1291-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51003
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.88.4.1291 PMC Full Text View journal details
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