Differential sensitivity to the anxiolytic effects of ethanol and flunitrazepam in PKC gamma null mutant mice

Tests of ethanol effects in PKC gamma null mutant mice have indicated that PKC gamma plays a role in initial sensitivity to ethanol-induced sedation, hypothermia, and GABA(A) receptor function and impacts neurochemical pathwa ys mediating anxiety. The present study was undertaken to evaluate whether the decreased sensitivity to ethanol previously observed in these mice gene ralized to the anxiolytic effects of ethanol. PKC gamma null mutant mice an d wild-type controls were tested in the elevated-plus maze, the black/white box, and the mirrored chamber after ethanol (0, 1.0, 1.25, 1.5 g/kg) or fl unitrazepam (FNZ) (0, 0.015, 0.03, 0.06 mg/kg). Results indicated that alth ough both genotypes exhibited anxiolytic responses to ethanol in the elevat ed plus-maze, null mutant mice were less sensitive than wild-type control m ice; however, in the black/white box, PKC gamma null mutants were more sens itive than controls to the anxiolytic effects of FNZ. Neither ethanol nor F NZ produced anxiolytic responses in the mirrored chamber for either genotyp e. These results suggest that PKC gamma differentially mediates anxiolytic responses to ethanol and FNZ and that this relationship interacts with each drug's efficacy in reducing anxiety-related behaviors specific to each of the three mazes. (C) 2001 Elsevier Science Inc. All rights reserved.