Reduced anxiety-like and depression-related behavior in neuropeptide Y Y4 receptor knockout mice
Open accessAbstract
Neuropeptide Y (NPY) acting through Y1 receptors reduces anxiety- and depression-like behavior in rodents, whereas Y2 receptor stimulation has the opposite effect. This study addressed the implication of Y4 receptors in emotional behavior by comparing female germ line Y4 knockout (Y4-/-) mice with control and germ line Y2-/- animals. Anxiety- and depression-like behavior was assessed with the open field (OF), elevated plus maze (EPM), stress-induced hyperthermia (SIH) and tail suspension tests (TST), respectively. Learning and memory were evaluated with the object recognition test (ORT). In the OF and EPM, both Y4-/- and Y2-/- mice exhibited reduced anxiety-related behavior and enhanced locomotor activity relative to control animals. Locomotor activity in a familiar environment was unchanged in Y4-/- but reduced in Y2-/- mice. The basal rectal temperature exhibited diurnal and genotype-related alterations. Control mice had temperature minima at noon and midnight, whereas Y4-/- and Y2-/- mice displayed only one temperature minimum at noon. The magnitude of SIH was related to time of the day and genotype in a complex manner. In the TST, the duration of immobility was significantly shorter in Y4-/- and Y2-/- mice than in controls. Object memory 6 h after initial exposure to the ORT was impaired in Y2-/- but not in Y4-/- mice, relative to control mice. These results show that genetic deletion of Y4 receptors, like that of Y2 receptors, reduces anxiety-like and depression-related behavior. Unlike Y2 receptor knockout, Y4 receptor knockout does not impair object memory. We propose that Y4 receptors play an important role in the regulation of behavioral homeostasis.
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The Y4 receptor, which is mainly activated by peripheral PP, modulates anxiety and fear-related disorders in rodents.
“The Y 4 receptor, which is mainly activated by peripheral PP, modulates anxiety and fear-related disorders in rodents [174,185,186].”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [186]
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“Recently Painsipp et al. (2008) demonstrated an anxiolytic and anti-depressant-like effect of Y4 receptor deletion in female mice.”
BackgroundResultPotential gut–brain mechanisms behind adverse mental health outcomes of bariatric surgery
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- Authors
- Painsipp, E., Wultsch, T., Edelsbrunner, M. E., Tasan, R. O., Singewald, N., Herzog, H., & Holzer, P.
- Affiliations
- Medical University of Graz (AT)
- Innsbruck Medical University (AT)
- Universität Innsbruck (AT)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Holzer, P.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2008-07
- Volume
- 7
- Issue
- 5
- Pages
- 532-542
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- PMC
- PMC4359911
- OpenAlex
- W2009185765
- Cited by
- 79
- References
- 63
- Citations by year
- 2024: 5 · 2023: 3 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 6 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- neuropeptide Y, Y4 receptor, Y2 receptor, anxiety-like behavior, depression-like behavior, receptor knockout mice, locomotor activity, stress-induced hyperthermia, tail suspension test, object recognition memory, rectal temperature, circadian rhythm
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Corticosterone, Depression, Exploratory Behavior, Female, Fever, Mice, Inbred C57BL, Stress, Physiological, Receptors, Neuropeptide Y, Mice, Knockout, Maze Learning, Recognition, Psychology, Mice
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