Publication Date:
1993-01-22
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wahlestedt, C -- Pich, E M -- Koob, G F -- Yee, F -- Heilig, M -- New York, N.Y. -- Science. 1993 Jan 22;259(5094):528-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8380941" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
*Anxiety
;
Base Sequence
;
Cells, Cultured
;
Cerebral Cortex/*physiology
;
Cyclic AMP/metabolism
;
Down-Regulation
;
Embryo, Mammalian
;
Learning
;
Male
;
Molecular Sequence Data
;
Neurons/drug effects/*physiology
;
Neuropeptide Y/*physiology
;
Oligodeoxyribonucleotides
;
Oligonucleotides, Antisense/*pharmacology
;
Polymerase Chain Reaction
;
Rats
;
Rats, Wistar
;
Receptors, Neuropeptide Y/*drug effects/*genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
