Galanin GAL-R1 Receptor Null Mutant Mice Display Increased Anxiety-Like Behavior Specific to the Elevated Plus-Maze

• DOI: 10.1038/sj.npp.1300164
• Publication Date: 2003-04-16T14:32:40Z
• Authors: Andrew Holmes; Jefferson W Kinney; Craige C Wrenn; Qian Li; Rebecca J Yang; Li Ma; Janani Vishwanath; Maria C Saavedra; Caitlin E Innerfield; Arie S Jacoby; John Shine; Tiina P Iismaa; Jacqueline N Crawley
• Keywords: Male; Mice, Knockout; Receptors, Neuropeptide; Galanin; Anxiety; Darkness; Motor Activity; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Exploratory Behavior; Animals; Maze Learning; Receptors, Galanin; Lighting

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.