Sensitization to the reinforcing effects of cocaine following binge-abstinent self-administration.

The process of addiction in humans involves a transition from recreational drug use to compulsive drug-taking. To understand or study this behavioral phenomenon from a neurobiological perspective, behavioral models that reflect this process are necessary. Data from typical (restricted access) self-administration procedures demonstrate a stable pattern of responding over time, and thus fail to capture the transitional phases of this process. Here we describe the development of a model that incorporates self-administration-induced changes in the reinforcing efficacy of cocaine, assessed using a progressive ratio schedule of reinforcement to probe the 'motivational' state of the animal. To date we have identified two necessary conditions for the development of this sensitization: extended access to cocaine and a deprivation period. This model, in conjunction with recently developed tools to characterize neurochemical and epigenetic changes, will provide a better understanding of the neurobiological bases of the addiction process.