PKCε and PKCγ knockout mice show differences in anxiety-like behavior compared with wild-type mice. PKCε knockout mice have decreased anxiety-like behavior and lower levels of stress hormones compared with wild-type mice, which may be due to increased sensitivity of their GABAA receptors to modulation by endogenous neurosteroids.212 PKCγ knockout mice also show decreased anxiety-like behavior compared with wild-type mice215 and are less sensitive to the anxiolytic effects of ethanol.216 However, PKCγ knockout mice show no differences in flunitrazepam-induced anxiolysis compared with wild-type mice,216 suggesting that the effect of PKCγ is specific to ethanol and not a general effect on other GABA modulators, as seen with the PKCε knockout mice. PKCγ knockout mice also show greater impulsivity than wild-type mice.217 Interestingly, genetic polymorphisms in PKCγ were recently associated with behavioral disinhibition, attention-deficit/hyperactivity disorder, and substance experimentation in one human genetic study.218
