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

Ric-8 is a guanine nucleotide exchange factor for a subset of G proteins and it is required to maintain Gq and the Gs 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 anxi ety and spatial learning. Based on these results we can conclude the importance of ric-8 in the regulation of memory and emotional behavior. © 2005 Elsevier B.V. All rights reserved.