Cocaine Seeking And Taking Are Oppositely Regulated By Dopamine

In some individuals, drug-associated cues subsume potent control of behavior, such as the elicitation of drug craving^1-3 and automatized drug use⁴. The intensity of this cue reactivity is highly predictive of relapse and other clinical outcomes in substance use disorders^5,6. It has been postulated that this cue reactivity is driven by augmentation of dopamine release over the course of chronic drug use⁷. Here we carried out longitudinal recording and manipulation of cue-evoked dopamine signaling across phases of substance-use related behavior in rats. We observed a subset of individuals that exhibited increased cue reactivity and escalated drug consumption, two cardinal features of substance use disorders. In these individuals, cue-evoked phasic dopamine release underwent diametrically opposed changes in amplitude, determined by the context in which the cue is presented. Dopamine evoked by non-contingent cue presentation increased over drug use, producing greater cue reactivity; whereas dopamine evoked by contingent cue presentation decreased over drug use, producing escalation of drug consumption. Therefore, despite being in opposite directions, these dopamine trajectories each promote core symptoms of substance use disorders.