PKCε and PKCγ knockout mice show opposite responses in ethanol self-administration paradigms. PKCε knockout mice self-administer less ethanol196,210 and have decreased preference for ethanol compared with wild-type mice.210 PKCε activity is decreased by mGluR5 antagonists,219 and systemic administration of the mGluR5 antagonist MPEP decreases ethanol consumption in wild-type mice but not in PKCε knockout mice.220 Restoration of neuronal PKCε activity by conditional gene expression of PKCε in knockout mice increases ethanol consumption to wild-type levels indicating that the effect of the PKCε null mutation on drinking is not due to a developmental abnormality but results instead from deficient PKCε signaling in the adult nervous system.211 In contrast to PKCε knockout mice, PKCγ knockout mice consume more ethanol than wild-type littermates.217
