[Background] Diazepam is mainly used for anxiolytic drug in human, but this drug is known to have undesirable adverse effects. Its anxiolytic effect and adverse effects show individual differences. It is believed that anxiety-like behaviors and sensitivity to drugs are quantitative traits that can be affected by multiple genes. In order to understand the mechanism by which diazepam affects differently among humans, it is necessary to understand genetic basis underlying differences in the effects. Wild-derived inbred mouse strains show high anxiety-like behaviors and they exhibit diversity in the level of anxiety among strains. Thus, the wild-derived mouse resource is very useful for identifying quantitative traits related to anxiety. In laboratory inbred strains of mouse, behavioral pharmacological tests with diazepam have been performed using open-field test, elevated plus maze test, and light/dark box test. In these experiments, the anxiolytic effect of diazepam is varied depending on test conditions and/or strains used. However, wild-derived moue strains have never been studied for the strain differences of sensitivity to diazepam.
[Objective] We aimed to establish a method for examining anxiolytic effect of diazepam, and tried to characterize strain differences of sensitivities to diazepam in wild-derived inbred strains and wild-derived heterogeneous stock mice (WHS).
[Method] Eight wild-derived inbred strains (MSM, HMI, BLG/2, PGN/2, KJR, CHD, NJL and BFM/2) and WHS, which are made by crossing these eight strains, are used for the study. Mice were injected with vehicle (1mg/kg) at first day and with diazepam (1mg/kg) at next day. Injections were performed 30min before the open-field test each day.
[Result] We found clear strain differences of sensitivity to diazepam in wild-derived strains, suggesting the WHS is highly useful to reveal genetic basis of diversity of sensitivities to diazepam.