Psychopharmacology

, Volume 195, Issue 4, pp 547–557

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

  • Rose-Marie Karlsson
  • Jessica S. Choe
  • Heather A. Cameron
  • Annika Thorsell
  • Jacqueline N. Crawley
  • Andrew Holmes
  • Markus Heilig
Original Investigation

DOI: 10.1007/s00213-007-0945-2

Cite this article as:
Karlsson, RM., Choe, J.S., Cameron, H.A. et al. Psychopharmacology (2008) 195: 547. doi:10.1007/s00213-007-0945-2

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.

Keywords

Neuropeptide Y Y1 Receptor Knockout Mouse Fear Anxiety Depression Neurogenesis 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Rose-Marie Karlsson
    • 1
    • 2
    • 3
  • Jessica S. Choe
    • 4
  • Heather A. Cameron
    • 4
  • Annika Thorsell
    • 1
  • Jacqueline N. Crawley
    • 5
  • Andrew Holmes
    • 3
  • Markus Heilig
    • 1
    • 2
  1. 1.Laboratory of Clinical and Translational Studies, NIHNational Institute of Alcohol Abuse and Alcoholism, NIHBethesdaUSA
  2. 2.Section of Psychiatry, Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
  3. 3.Section of Behavioral Science and Genetics, Laboratory of Integrative NeuroscienceNational Institute of Alcohol Abuse and Alcoholism, NIHBethesdaUSA
  4. 4.Unit of Neuroplasticity, Mood and Anxiety Disorders ProgramNational Institute of Mental Health, NIHBethesdaUSA
  5. 5.Laboratory of Behavioral NeuroscienceNational Institute of Mental Health, NIHBethesdaUSA

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