The protein kinases reviewed here have numerous downstream effects resulting in changes in gene transcription and protein synthesis that contribute to long-term changes in neural networks involved in addiction-related behavior. Several general conclusions may be drawn regarding the role of protein kinases in behavior related to drugs of abuse. Inhibition of ERK and CaMKII may be beneficial in reducing relapse for psychostimulants and opiates. For most drugs of abuse, inhibition of PKA decreases both drug self-administration and signs of drug withdrawal. For ethanol, however, increasing PKA activity in the central amygdala decreases self-administration and withdrawal-induced anxiety, and these responses may be mediated by increased expression of NPY and BDNF in that brain region. In contrast, deletion of PKCε increases sensitivity to ethanol and morphine and markedly decreases ethanol self-administration. Cdk5 appears to negatively regulate responding for cocaine and cocaine reward, suggesting that strategies designed to activate Cdk5 may be useful to treat cocaine addiction. Although Fyn appears to contribute to acute tolerance to the intoxicating effects of ethanol, data on Fyn regulation of ethanol self-administration remain inconclusive. Overall, protein kinase
