PKC knockout mice have been useful in determining the role of PKC isozymes in ethanol-related behaviors. Administration of high concentrations of ethanol (3.2–4 g/kg) produces hypnosis and anesthesia, which can be measured as the loss of righting reflex (LORR) in rodents. PKCε knockout mice show an increased duration of the ethanol-induced LORR210 that is due to decreased acute functional tolerance to ethanol.188 PKCε knockout mice also show increased duration of LORR induced by pentobarbital, pregnanolone, or benzodiazepines.210–212 Restoration of PKCε activity by conditional gene expression of PKCε in knockout mice reduces ethanol- and pentobarbital-induced LORR to wild-type levels.211 In contrast to PKCε knockout mice, PKCγ knockout mice show a reduced duration of ethanol-induced LORR compared with wild-type mice.213 Unlike with PKCε knockout mice, this change in LORR duration appears specific for ethanol since PKCγ knockout mice show no differences in pentobarbital-induced LORR.213 PKCγ knockout mice also do not develop tolerance to ethanol-induced LORR or hypothermia on some genetic backgrounds.214
