Abstract:
RATIONALE:Neuropeptide Y (NPY) is implicated in the pathophysiology of affective illness. Multiple receptor subtypes (Y1R, Y2R, and Y5R) have been suggested to contribute to NPY's effects on rodent anxiety and depression-related behaviors. OBJECTIVES:To further elucidate the role of Y1R in (1) NPY's anxiolytic-like effects and (2) fluoxetine's antidepressant-like and neurogenesis-inducing effects. METHODS:Mice lacking Y1R were assessed for spontaneous anxiety-like behavior (open field, elevated plus-maze, and light/dark exploration test) and Pavlovian fear conditioning, and for the anxiolytic-like effects of intracerebroventricularly (icv)-administrated NPY (elevated plus-maze). Next, Y1R -/- were assessed for the antidepressant-like effects of acute fluoxetine in the forced swim test and chronic fluoxetine in the novelty-induced hypophagia test, as well as for chronic fluoxetine-induced hippocampal neurogenesis. RESULTS:Y1R -/- exhibited largely normal baseline behavior as compared to +/+ littermate controls. Intraventricular administration of NPY in Y1R -/- mice failed to produce the normal anxiolytic-like effect in the elevated plus-maze test seen in +/+ mice. Y1R mutant mice showed higher immobility in the forced swim test and longer latencies in the novelty-induced hypophagia test. In addition, Y1R -/- mice responded normally to the acute and chronic effects of fluoxetine treatment in the forced swim test and the novelty-induced hypophagia test, respectively, as well as increased neuronal precursor cell proliferation in the hippocampus. CONCLUSIONS:These data demonstrate that Y1R is necessary for the anxiolytic-like effects of icv NPY, but not for the antidepressant-like or neurogenesis-inducing effects of fluoxetine. The present study supports targeting Y1R as a novel therapeutic target for anxiety disorders.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Karlsson RM,Choe JS,Cameron HA,Thorsell A,Crawley JN,Holmes A,Heilig Mdoi
10.1007/s00213-007-0945-2subject
Has Abstractpub_date
2008-01-01 00:00:00pages
547-57issue
4eissn
0033-3158issn
1432-2072journal_volume
195pub_type
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journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244082
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journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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