Galanin GAL-RI receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze

The neuropeptide galanin coexists with norepinephrine and serotonin in neuralsystems 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 nullmutation in the Galr1 gene. GAL-R1 —/— are viable and show no abnormalities in health, neurologicalreflexes, 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 nullmutant mice and +/+ controls. Principalcomponents factor analysis of behavioralscores 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 normalC57BL/6J mice. These behavioralfindings in the first galanin receptor nullmutant mouse are consistent with the hypothesis that galanin exerts anxiolytic actions via the GAL-R1 receptor under conditions of relatively high stress.