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Involvement of a c-fos-dependent mechanism in caffeine-induced expression of the preprotachykinin A and neurotensin/neuromedin N genes in rat striatum.
- Source :
-
The European journal of neuroscience [Eur J Neurosci] 1997 Oct; Vol. 9 (10), pp. 2135-41. - Publication Year :
- 1997
-
Abstract
- Striatal c-fos induction was blocked by local administration of phosphorothioated c-fos antisense oligonucleotides (AS-ODN) to examine the possible role of caffeine-induced c-fos expression in transcriptional regulation of striatal preproenkephalin, prodynorphin, preprotachykinin A and neurotensin/neuromedin N. Caffeine (100 mg/kg i.p.) induced both c-fos mRNA and Fos-protein, and this induction was significantly attenuated by intrastriatal injection of 4 (but not 1) nmol c-fos AS-ODN. This suggests that, in addition to translational arrest, other mechanisms may be involved in the mediation of antisense action. The action of the AS-ODN was sequence specific. The antisense blockade of c-fos reduced the effect of caffeine on the expression of mRNAs for preprotachykinin A and neurotensin/neuromedin N in the ventrolateral caudate-putamen. Levels of preproenkephalin and prodynorphin transcripts were unaffected. Thus caffeine induction of striatal preprotachykinin A mRNA and neurotensin/neuromedin N mRNA, but not of preproenkephalin mRNA or prodynorphin mRNA, may at least in part be mediated by a pathway involving Fos protein. The findings illustrate the utility of blockade of gene expression with antisense oligonucleotides for in vivo studies of drug actions.
- Subjects :
- Animals
Corpus Striatum drug effects
Enkephalins biosynthesis
Gene Expression Regulation drug effects
Male
PC12 Cells
Proto-Oncogene Proteins c-fos biosynthesis
RNA, Messenger biosynthesis
Rats
Rats, Sprague-Dawley
Thionucleotides
Caffeine pharmacology
Corpus Striatum physiology
Genes, fos
Neurotensin biosynthesis
Oligonucleotides, Antisense pharmacology
Peptide Fragments biosynthesis
Protein Precursors biosynthesis
Tachykinins biosynthesis
Transcription, Genetic drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0953-816X
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The European journal of neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 9421173
- Full Text :
- https://doi.org/10.1111/j.1460-9568.1997.tb01380.x