Cocaine induces striatal c-fos-immunoreactive proteins via dopaminergic D1 receptors.
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.
Young
S T
ST
Laboratory of Cerebral Metabolism, National Institutes of Mental Health, National Institutes of Health, Bethesda, MD 20892.
Porrino
L J
LJ
Iadarola
M J
MJ
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D001552:Benzazepines / Q000494:pharmacology; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism; D004790:Enzyme Induction; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos; D011699:Putamen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1; D012016:Reference Values; D013469:Sulpiride / Q000494:pharmacology
D000906:Antibodies; D001552:Benzazepines; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013469:Sulpiride; D011505:Protein-Tyrosine Kinases; D003042:Cocaine