The development of addiction involves pathological drug-induced changes in cellular and molecular mechanisms of synaptic plasticity that underlie normal learning and memory.1–3 Common neuronal pathways and molecular adaptations to different drugs of abuse in the limbic system have been identified.4 Recently, a large genetic meta-analysis has identified some common genes and signaling pathways in drug addiction, and protein kinases are central components in this postulated common molecular network.5 Abused drugs stimulate signaling pathways that activate protein kinases, leading to altered gene transcription and protein synthesis, which contribute to long-term changes in synaptic function and neural networks that ultimately result in addiction. Here we review some of the best-studied protein kinases that appear to be pivotal in addiction: extracellular signal-regulated kinase, cAMP-dependent protein kinase, cyclin-dependent protein kinase 5, protein kinase C, calcium/calmodulin-dependent protein kinase II, and Fyn tyrosine kinase. These protein kinases are all widely expressed throughout the brain and in the limbic system.6
