Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze.
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.
Holmes
Andrew
A
Section on Behavioral Genomics, National Institute of Mental Health, NIH, Bethesda, MD 20892, USA. aholmes@intra.nimh.nih.gov
Kinney
Jefferson W
JW
Wrenn
Craige C
CC
Li
Qian
Q
Yang
Rebecca J
RJ
Ma
Li
L
Vishwanath
Janani
J
Saavedra
Maria C
MC
Innerfield
Caitlin E
CE
Jacoby
Arie S
AS
Shine
John
J
Iismaa
Tiina P
TP
Crawley
Jacqueline N
JN
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
D044088:Receptors, Galanin; D018013:Receptors, Neuropeptide; D019004:Galanin