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Biol Psychiatry. 2014 Dec 1;76(11):840-9. doi: 10.1016/j.biopsych.2014.01.009. Epub 2014 Jan 24.

Conditional inactivation of neuropeptide Y Y1 receptors unravels the role of Y1 and Y5 receptors coexpressing neurons in anxiety.

Author information

  • 1Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (AL, PM, IB, AO, CE), Orbassano (Turin); Department of Neuroscience (AL, PM, IB, AO, CE).
  • 2Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (AL, PM, IB, AO, CE), Orbassano (Turin); Neuroscience Institute of Turin (AO, CE); Department of Neuroscience (AL, PM, IB, AO, CE).
  • 3Departments of Anatomy, Pharmacology, and Forensic Medicine (ABac), University of Turin, Turin, Italy.
  • 4Department of Integrative Biology and Physiology (ABar), University of Minnesota, Minneapolis, Minnesota.
  • 5Department of Evolutionary and Functional Biology (PP), University of Parma, Parma, Italy.
  • 6Department of Molecular Neurobiology (RS), Max Planck Institute for Medical Research, Heidelberg, Germany.
  • 7Neuroscience Institute of the Cavalieri-Ottolenghi Foundation (AL, PM, IB, AO, CE), Orbassano (Turin); Neuroscience Institute of Turin (AO, CE); Department of Neuroscience (AL, PM, IB, AO, CE). Electronic address: carola.eva@unito.it.

Abstract

BACKGROUND:

The Y1 receptor (Y1R) and Y5 receptor (Y5R) for neuropeptide Y share similar actions in the regulation of anxiety. Previously demonstrated that conditional removal of the Y1R during postnatal development in the forebrain excitatory neurons leads to higher anxiety, increased hypothalamus-pituitary-adrenocortical axis activity, and decreased body growth rate in male mice raised by foster mothers that exhibit high levels of maternal care. In the present study, we used the same conditional system to analyze the specific contribution to emotional behavior and stress response of the Y1R coexpressed with the Y5R.

METHODS:

Using the Cre-loxP recombination system, we investigated anxious behavior, spatial memory, and metabolic functions of conditional knockout mice in which the inactivation of the Npy1r gene was induced in the Y5Rs expressing neurons of juvenile mice (Npy1r(Y5R-/-) ).

RESULTS:

Npy1r(Y5R-/-) mice show increased anxiety-related behavior but no changes in hypothalamus-pituitary-adrenocortical axis activity or in body weight growth, independently of gender and mouse strain used as foster mothers. Also, Npy1r(Y5R-/-) mice of both genders display increased spatial reference memory in the Morris water maze test.

CONCLUSIONS:

The results suggest that neuropeptide Y Y1R differentially expressed in the limbic system regulates anxiety and stress responses via distinct neurochemical circuits. In addition, we provide the first experimental genetic evidence that the Y1Rs coexpressed with the Y5R are involved in retention of spatial memory in male and female mice.

Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Behavioral flexibility; Cre-loxP system; GABA; conditional knockout mice; hypothalamus-pituitary-adrenocortical axis; spatial memory

PMID:
24548641
[PubMed - in process]
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