GENOTYPIC DIFFERENCES BETWEEN C57BL 6 AND A-INBRED MICE IN ANXIOLYTICAND SEDATIVE ACTIONS OF DIAZEPAM/

The role of genotype in susceptibility to the behavioral actions of be nzodiazepines is not well characterized. To develop a model for such s tudies, we have characterized the anxiolytic and sedative activities o f diazepam in C57BL/6J and A/J inbred mice. C57BL/6J mice were more re sponsive than A/J mice to diazepam-induced anxiolytic-like activity in the mirrored chamber aversion assay and the elevated plus-maze assay. Basal activity of the two strains did not differ in either assay. In contrast, the two strains were equally responsive to the anxiolytic ef fects of the 5-HT1A receptor partial agonist, buspirone. C57BL/6J mice were also more susceptible to the sedative effects of diazepam than w ere A/J mice. Flumazenil blocked the effects of diazepam in these beha vioral assays. Measurement of diazepam and nordiazepam in blood and br ain suggested that the response differences are of a pharmacodynamic r ather than a pharmacokinetic nature. Taken together, these findings in dicate that C57BL/6J and A/J mice provide a valuable tool for behavior al genetic studies of the mechanisms underlying the pharmacological ac tions of benzodiazepines.