Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides

Claes Wahlestedt, Emilio Merlo Pich, George F. Koob, Frances Yee, Markus Heilig

Research output: Contribution to journalArticlepeer-review

508 Scopus citations

Abstract

The function of neuropeptide Y, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists An antisense oligodeoxynucleotide corresponding to the NH2-terminus of the rat Y1 receptor was constructed and added to cultures of rat cortical neurons. This treatment resulted in a reduced density of Y1 (but not Y2) receptors and diminished the decrease in adenosine 3′,5′-monophosphate (cAMP) usually seen after Y1 receptor activation. Repeated injection of the same oligodeoxynucleotide into the lateral cerebral ventricle of rats was followed by a similar reduction of cortical Y1 (but not Y2) receptors. Such antisense-treated animals displayed behavioral signs of anxiety. Thus, specific inhibition of neurotransmitter receptor expression can be accomplished in the living brain and demonstrates that altered central neuropeptide Y transmission produces an anxiety-like state.

Original languageEnglish (US)
Pages (from-to)528-531
Number of pages4
JournalScience
Volume259
Issue number5094
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • General

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