Addiction as a Pathology in Prefrontal Cortical Regulation of Corticostriatal Habit Circuitry

It has been proposed that the progressive development of addiction from social use into a compulsive relapsing disorder results from a decrease in executive control over behavior and/or a strengthening of cortico-striatal habit circuitry. Based upon a review of the literature using the reinstatement model of drug relapse in rodents, it will be proposed that a transition between executive prefrontal cortical regulation of relapse to cortico-striatal habit circuitry can be modeled in animals trained to self-administer cocaine. Accordingly, prefrontal regulation of the reinstatement of cocaine-seeking can be modeled by extinguishing the animals, thereby engaging cortical circuitry. In contrast, if animals are placed in forced abstinence, the prefrontal cortex is not as fully engaged when the animal is returned to the cocaine context to seek drug. In parallel with distinctions between the circuitry involved in abstinent versus extinguished subjects, the magnitude of reinstatement is greater in animals placed in abstinence versus undergoing extinction training, and reinstatement progressively increases with the duration of forced abstinence. These findings will be described and integrated relative to modeling the transition from regulated relapse (social use) to compulsive (addicted) relapse.