Back to Search Start Over

Involvement of a c-fos-dependent mechanism in caffeine-induced expression of the preprotachykinin A and neurotensin/neuromedin N genes in rat striatum.

Authors :
Svenningsson P
Georgieva J
Kontny E
Heilig M
Fredholm BB
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.

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