Prior Cocaine Exposure Increases Firing to Immediate Reward While Attenuating Cue and Context Signals Related to Reward Value in the Insula.

Abstract

The insula contributes to behavioral control and is disrupted by substance abuse, yet we know little about the neural signals underlying these functions or how they are disrupted after chronic drug self-administration. Here, male and female rats self-administered either cocaine (experimental group) or sucrose (control) for 12 consecutive days. After a 1 month withdrawal period, we recorded from insula while rats performed a previously learned reward-guided decision-making task. Cocaine-exposed rats were more sensitive to value manipulations and were faster to respond. These behavioral changes were accompanied by elevated counts of neurons in the insula that increased firing to reward. These neurons also fired more strongly at the start of long-delay trials, when a more immediate reward would be expected, and fired less strongly in anticipation of the actual delivery of delayed rewards. Although reward-related firing to immediate reward was enhanced after cocaine self-administration, reward-predicting cue and context signals were attenuated. In addition to revealing novel firing patterns unique to insula, our data suggest changes in such neural activity likely contribute to impaired decision making observed after drug use.SIGNIFICANCE STATEMENT The insula plays a clear role in drug addiction and drug-induced impairments of decision making, yet there is little understanding of its underlying neural signals. We found that chronic cocaine self-administration reduces cue and context encoding in insula while enhancing signals related to immediate reward. These changes in neural activity likely contribute to impaired decision making and impulsivity observed after drug use.