Galanin GAL-R1 Receptor Null Mutant Mice Display Increased Anxiety-Like Behavior Specific to the Elevated Plus-Maze
Abstract
The neuropeptide galanin coexists with norepinephrine and serotonin in neural systems mediating emotion. Previous findings suggested that galanin modulates anxiety-related behaviors in rodents. Three galanin receptor subtypes have been cloned; however, understanding their functions has been limited by the lack of galanin receptor subtype-selective ligands. To study the role of the galanin GAL-R1 receptor subtype in mediating anxiety-related behavior, we generated mice with a null mutation in the Galr1 gene. GAL-R1 -/- are viable and show no abnormalities in health, neurological reflexes, motoric functions, or sensory abilities. On a battery of tests for anxiety-like behavior, GAL-R1 -/- showed increased anxiety-like behavior on the elevated plus-maze test. Anxiety-related behaviors on the light/dark exploration, emergence, and open field tests were normal in GAL-R1 -/-. This test-specific anxiety-like phenotype was confirmed in a second, independent cohort of GAL-R1 null mutant mice and +/+ controls. Principal components factor analysis of behavioral scores from 279 mice suggested that anxiety-like behavior on the elevated plus-maze was qualitatively distinct from behavior on other tests in the battery. In addition, exposure to the elevated plus-maze produced a significantly greater neuroendocrine response than exposure to the light/dark exploration test, as analyzed in normal C57BL/6J mice. These behavioral findings in the first galanin receptor null mutant mouse are consistent with the hypothesis that galanin exerts anxiolytic actions via the GAL-R1 receptor under conditions of relatively high stress.
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Time spent in the habituated center chamber provided a preliminary measure of anxiety-like behaviors.
“In addition, time spent in the habituated center chamber provided a preliminary measure of anxietylike behaviors, analogous to the open field emergence test (Holmes et al. 2003;Smith et al. 1998).”
From Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice (2004) · cites this paper as Holmes et al. 2003
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- Authors
- Holmes, A., Kinney, J. W., Wrenn, C. C., Li, Q., Yang, R. J., Ma, L., Vishwanath, J., Saavedra, M. C., Innerfield, C. E., Jacoby, A. S., Shine, J., Iismaa, T. P., & Crawley, J. N.
- Affiliations
- National Institutes of Health (US)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Holmes, Andrew
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2003-01-13
- Volume
- 28
- Issue
- 6
- Pages
- 1031-1044
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2067681628
- Cited by
- 202
- References
- 2
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 11 · 2021: 6 · 2020: 6 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 10
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- galanin, anxiety-like behavior, elevated plus maze, anxiolytic effects, neuroendocrine response, stress, neuropeptides, norepinephrine, serotonin, emotion regulation
- MeSH terms
- Animals, Anxiety, Darkness, Exploratory Behavior, Lighting, Male, Mice, Inbred C57BL, Motor Activity, Receptors, Neuropeptide, Mice, Knockout, Maze Learning, Galanin, Receptors, Galanin, Mice
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