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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.

Type Journal
ISBN 0893-133X (Print)
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. :
Garvan Authors Prof John Shine
Published Date 2003-01-01 00:00:00
Published Volume 28
Published Issue 6
Published Pages 1031-44
Status Published In-print