Incubation of Accumbal Neuronal Reactivity to Cocaine Cues During Abstinence Predicts Individual Vulnerability to Relapse

Abstract

An important goal for the treatment of cocaine addiction is to identify neuromarkers that can predict individual vulnerability to relapse after abstinence. There is some evidence that individual reactivity to cue-induced craving may predict subsequent relapse after a period of abstinence. Here we sought to identify the neuronal correlates of this predictive relationship in rats. Rats were trained to self-administer cocaine (6 h) for 16 days to induce escalation of cocaine intake. Then rats underwent a 1-month period of forced abstinence after which they were re-exposed to cocaine self-administration (6 h) for 8 additional days to induce re-escalation of cocaine intake. We recorded nucleus accumbens (NAc) neuronal responses to drug conditioned stimuli (CS) 1 day before and after 1 month of abstinence from cocaine intake escalation. Rats were ranked according to their individual percentage of CS responsive neurons recorded during the last day of abstinence and split by the median into two groups. We found evidence for a robust, incubation-like increase in NAc reactivity to cocaine cues after abstinence only in a subset of individuals (High CS rats). Importantly, compared with other rats that did not present an incubation of NAc reactivity to cocaine cues (Low CS rats), High CS rats were faster to re-escalate their intake of cocaine after abstinence. In addition, after re-escalation, they worked harder and were less sensitive to risk of punishment than Low CS rats, indicating a strengthened motivation to seek and/or take the drug in that group of rats. Overall, these findings indicate that incubation of NAc neuronal reactivity to cocaine cues during abstinence may constitute a predictive neuromarker for individual vulnerability to relapse.