Although there is a strong genetic component to vulnerability, at its root addiction to cocaine and other drugs of abuse is considered a drug-induced disorder of neuroplasticity.43,45-55 Indeed, cocaine addiction can be conceptualized as a disorder in which excessive cocaine consumption, in conjunction with genetic and environmental influences, manifests enduring neuroplasticity in brain circuitries that regulate reward and cognitive and emotional processing, and it is this plasticity that drives compulsive drug seeking. With the emerging appreciation that maladaptive neuroplasticity mechanisms drive addiction, much emphasis has been placed on such adaptations in addiction-related brain areas. In particular, considering that cocaine and all other major drugs of abuse increase dopamine transmission in the mesocorticolimbic system,56 dopamine-dependent plasticity in mesocorticolimbic neurons has been a major focus of investigation. Nestler and colleagues have shown that cocaine engages “epigenetic” machinery in brain reward circuitries, and that this action influences gene expression in response to cocaine and thereby controls behavioral responses to the drug. Indeed, chromatin immunoprecipitation (ChIP) assays from mouse striatal tissues have revealed that chronic cocaine treatment induced marked increases in acetylation state of
