Heterozygous mice with Ric-8 mutation exhibit impaired spatial memory and decreased anxiety

Behav Brain Res. 2006 Feb 15;167(1):42-8. doi: 10.1016/j.bbr.2005.08.025. Epub 2005 Oct 10.

Abstract

Ric-8 is a guanine nucleotide exchange factor for a subset of Galpha proteins and it is required to maintain Galpha(q) and the Galpha(s) pathways in functional state. In adult mice Ric-8 is expressed in regions involved in the regulation of behavior (neocortex, cingulate cortex and hippocampus). As Ric-8 is shown to regulate neuronal transmitter release, the aim of present study was to perform behavioral analysis of ric-8 mutant. Homozygous (-/-) ric-8 mutant mice are not viable and die in early embryonic development, therefore for behavioral analysis heterozygous (+/-) ric-8 mutant mice were used. We found decreased anxiety of ric-8 heterozygous mice in light-dark compartment test where mutant mice significantly avoided the light compartment. In spatial learning paradigm (Morris water maze) the performance of ric-8 (+/-) mice was impaired. Namely, in the reversal test, ric-8 (+/-) mice exhibited significant delay to find the hidden platform compared to wild-type (wt) littermates. We did not find differences in the behavioral tests reflecting the motor abilities of mice (motor activity, rota-rod). Therefore, described alterations seem to be specific for anxiety and spatial learning. Based on these results we can conclude the importance of ric-8 in the regulation of memory and emotional behavior.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Behavior, Animal / physiology
  • Exploratory Behavior / physiology
  • Female
  • Galactosides / metabolism
  • Guanine Nucleotide Exchange Factors
  • Hippocampus / pathology
  • Indoles / metabolism
  • Male
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / genetics
  • Mutation*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics*
  • Pyramidal Cells / pathology
  • Reaction Time / genetics
  • Rotarod Performance Test / methods
  • Spatial Behavior / physiology*

Substances

  • Galactosides
  • Guanine Nucleotide Exchange Factors
  • Indoles
  • Nuclear Proteins
  • Ric8a protein, mouse
  • 5-bromo-4-chloro-3-indolyl beta-galactoside