PMID- 17891380
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20181113
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 195
IP  - 4
DP  - 2008 Jan
TI  - 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.
PG  - 547-57
AB  - 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.
FAU - Karlsson, Rose-Marie
AU  - Karlsson RM
AD  - Laboratory of Clinical and Translational Studies, NIH, National Institute of 
      Alcohol Abuse and Alcoholism, NIH, 10 Center Drive, 1-15330, Bethesda, MD 
      20892-1375, USA. karlssonr@mail.nih.gov
FAU - Choe, Jessica S
AU  - Choe JS
FAU - Cameron, Heather A
AU  - Cameron HA
FAU - Thorsell, Annika
AU  - Thorsell A
FAU - Crawley, Jacqueline N
AU  - Crawley JN
FAU - Holmes, Andrew
AU  - Holmes A
FAU - Heilig, Markus
AU  - Heilig M
LA  - eng
GR  - NH002784/NH/NIH HHS/United States
GR  - NH02177/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070922
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Receptors, Neuropeptide Y)
RN  - 0 (neuropeptide Y-Y1 receptor)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/*pharmacology
MH  - Anxiety/*physiopathology
MH  - Arousal/drug effects/physiology
MH  - Cell Count
MH  - Cell Division/drug effects/physiology
MH  - Conditioning, Classical/drug effects/physiology
MH  - Depression/*physiopathology
MH  - Fear/drug effects/physiology
MH  - Female
MH  - Fluoxetine/*pharmacology
MH  - Hippocampus/drug effects/physiopathology
MH  - Injections, Intraventricular
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/drug effects/physiology
MH  - Neuropeptide Y/pharmacology/*physiology
MH  - Receptors, Neuropeptide Y/*drug effects/genetics/physiology
EDAT- 2007/09/25 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/09/25 09:00
PHST- 2007/07/04 00:00 [received]
PHST- 2007/09/05 00:00 [accepted]
PHST- 2007/09/25 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/09/25 09:00 [entrez]
AID - 10.1007/s00213-007-0945-2 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2008 Jan;195(4):547-57. doi: 
      10.1007/s00213-007-0945-2. Epub 2007 Sep 22.