The neuropeptide Y Y1 receptor subtype is necessary for the anxiolytic-like effects of neuropeptide Y, but not the antidepressant-like effects of fluoxetine, in mice
2008 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 195, no 4, 547-557 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
Springer, 2008. Vol. 195, no 4, 547-557 p.
Neuropeptide Y, Y1, Receptor, Knockout, Mouse, Fear, Anxiety, Depression, Neurogenesis
IdentifiersURN: urn:nbn:se:liu:diva-101852DOI: 10.1007/s00213-007-0945-2PubMedID: 17891380OAI: oai:DiVA.org:liu-101852DiVA: diva2:666719