Escalation of Cocaine Intake and Incubation of Cocaine Seeking Are Correlated with Dissociable Neuronal Processes in Different Accumbens Subregions

Background: Cocaine addiction is characterized by a progressive increase in drug intake and a persistent craving for the drug during prolonged abstinence. Whether these two prominent features of cocaine addiction are related to each other and are mediated by similar or different neuronal processes is currently unknown. Methods: Rats were first allowed to self-administer cocaine under long-access (6-hour) conditions to induce escalation of cocaine intake. Self-administration sessions were designed to measure both drug seeking and drug taking. After escalation, rats underwent a 1-month period of forced abstinence after which they were re-exposed to cocaine to induce re-escalation of cocaine intake. In vivo electrophysiologic recordings were conducted in the core and shell subregions of the nucleus accumbens (NAc) during cocaine intake escalation, after abstinence and during re-escalation. Results: After abstinence, escalated levels of cocaine taking decreased toward pre-escalation levels, whereas cocaine seeking increased persistently. These opposite postabstinence changes were uncorrelated. At the neuronal level, the postabstinence decrease in cocaine taking was correlated with a normalization of depressed neuronal activity in the NAc shell that had developed during escalation of cocaine intake. In contrast, the incubation-like increase in cocaine seeking was selectively correlated with a persistent increase in the proportion of neurons in the NAc core that phasically fire during cocaine seeking. Conclusions: These findings show that cocaine taking and cocaine seeking evolve differently during abstinence from extended drug use and depend on dissociable neuronal processes in different subregions of the nucleus accumbens.