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Science 22 January 1993:
Vol. 259. no. 5094, pp. 528 - 531
DOI: 10.1126/science.8380941
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Articles

Science, Vol 259, Issue 5094, 528-531
Copyright © 1993 by American Association for the Advancement of Science

articles

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

C Wahlestedt, EM Pich, GF Koob, F Yee, and M Heilig

Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.

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.


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