title: 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.
authors.affiliation: Section on Behavioral Genomics, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. aholmes@intra.nimh.nih.gov
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
authors.forename: Jefferson W
authors.initials: JW
authors.lastname: Kinney
authors.forename: Craige C
authors.initials: CC
authors.lastname: Wrenn
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Janani
authors.initials: J
authors.lastname: Vishwanath
authors.forename: Maria C
authors.initials: MC
authors.lastname: Saavedra
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Innerfield
authors.forename: Arie S
authors.initials: AS
authors.lastname: Jacoby
authors.forename: John
authors.initials: J
authors.lastname: Shine
authors.forename: Tiina P
authors.initials: TP
authors.lastname: Iismaa
authors.forename: Jacqueline N
authors.initials: JN
authors.lastname: Crawley
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D003624:Darkness; D005106:Exploratory Behavior / Q000502:physiology; D019004:Galanin / Q000378:metabolism* / Q000502:physiology; D008029:Lighting; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D019004:Galanin