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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
Author(s) -
Svenningsson Per,
Georgieva Jeanette,
Kontnyi Ewa,
Heilig Markus,
Fredholm Bertil B.
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01380.x
Subject(s) - dynorphin , neurotensin , neuropeptide , endocrinology , medicine , substance p , enkephalin , striatum , chemistry , biology , opioid peptide , receptor , dopamine , opioid
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.