High Impulsivity Predicts Relapse to Cocaine-Seeking After Punishment-Induced Abstinence

Background: Relapse is a hallmark feature of cocaine addiction and a main challenge for treatment strategies. Human studies indicate a link between impulsivity and increased susceptibility to relapse. Methods: Rats were screened for high (HI) and low impulsivity (LI) on the 5-choice serial reaction time task. The HI and LI rats were trained to self-administer cocaine under a seeking-taking chained schedule: responses on the seeking lever resulted in presentation of the taking lever, responding upon which resulted in cocaine reinforcement. After the establishment of stable responding, an intermittent punishment schedule was introduced: completion of the seeking link resulted in the random presentation of either the taking lever or a mild footshock. This resulted in a progressive decrease in cocaine-seeking approaching abstinence. Relapse was assessed 7 days after punishment, during which responding on the seeking lever resulted in the presentation of the cocaine-associated stimuli (i.e., in the absence of cocaine or footshock). Results: The HI and LI animals significantly reinstated the cocaine-seeking response after a single phase of seeking punishment. However, after a second punishment phase only the HI rats reinitiated suppressed seeking responses and relapsed, an effect that was facilitated by prior extended cocaine access. In a preliminary study we found that the selective noradrenaline reuptake inhibitor, atomoxetine, a drug known to reduce impulsivity, prevented the reinstatement of cocaine-seeking. Conclusions: Impulsivity pre-dating drug abuse increases the susceptibility to relapse after abstinence. Medications targeting impulsivity might have utility as treatment interventions for relapse prevention and the promotion of abstinence.