Pattern of Intake and Drug Craving Predict the Development of Cocaine Addiction-like Behavior in Rats

Background: Clinical observations suggest that cocaine addiction often emerges with new patterns of use. Whether these changes are a cause of addiction or its consequence is unknown. We investigated whether the development of an addiction-like behavior in the rat is associated with the pattern of cocaine intake and with cocaine craving, a major feature of cocaine addiction. Methods: To determine whether changes in the pattern of cocaine use and enhanced craving precede or parallel the onset of addiction, we used a rat addiction model that incorporates core features of human addiction. For this purpose, the pattern of inter-infusion intervals (a measure of pattern of cocaine intake), sensitivity to cocaine-induced reinstatement (a measure of cocaine craving), and addiction-like behaviour were assessed over several months of intravenous cocaine self-administration. Results: We found that, even at early stages of cocaine self-administration, both the pattern of cocaine intake and the intensity of drug-induced reinstatement predict the severity of cocaine use, measured after 75 days of self-administration. Conclusions: Our results identify key predictors of cocaine addiction-intensified pattern of drug use and high drug-induced craving-that may help in the identification of subjects at risk for subsequent development of severe cocaine addiction.