Protein kinase C and alcohol addiction.

Alcohol abuse and addiction are serious global health problems. Tackling these disorders requires an understanding of how ethanol produces its effects. Early cell culture studies implicated the protein kinase C (PKC) family of serine-threonine kinases in mediating both acute and chronic responses to ethanol exposure. More recent studies using transgenic mice have identified two isozymes, PKCgamma and PKCepsilon, that have opposing roles in mediating the behavioral effects of ethanol. Genetic deletion of PKCgamma produces mice with a high ethanol drinking phenotype which are impulsive and require high levels of ethanol to reach intoxication, perhaps modeling the human condition of individuals who are at risk for developing alcoholism. In contrast, deletion of PKCepsilon produces a low ethanol drinking animal that is more sensitive to the acute effects of ethanol and displays less anxiety-like behavior, perhaps modeling human individuals with decreased risk for developing alcoholism. These findings suggest that drugs targeting PKCgamma and PKCepsilon may be useful to curb excessive drinking, the key symptom of alcohol use disorders.