Factors that influence the conditioned reinforcing effects of a cocaine-associated stimulus

Cocaine-associated stimuli acquire conditioned reinforcing effects and can precipitate relapse. We used the New Response Acquisition procedure to examine factors that influenced the conditioned reinforcing effects of cocaine-associated stimuli in rats. According to this procedure, rats first experienced Pavlovian conditioning, during which they were exposed to intravenous cocaine deliveries and stimulus (light + white noise) presentations. After Pavlovian conditioning, animals learned to respond to the cocaine-paired stimulus alone. The number of responses made for that stimulus reflected the conditioned reinforcing effects of the cocaine-associated stimulus. Across 3 experiments, the extent to which the dose of cocaine during Pavlovian conditioning (experiment 1), food restriction (experiment 2), and the number of cocaine-stimulus pairings and the number of days of Pavlovian conditioning (experiment 3) led to different conditioned reinforcing effects of the cocaine-associated stimulus. Taken together, we found that cocaine-associated cues took on conditioned reinforcing effects dose-dependently, were augmented by food restriction, and were most robust following 10 days of Pavlovian conditioning relative to 5 days of conditioning. These findings advance our understanding of the conditions under which cocaine-associated stimuli can act as a conditioned reinforcer. SIGNIFICANCE STATEMENT: Cocaine-associated stimuli acquire conditioned reinforcing effects via Pavlovian conditioning that drive drug-seeking and relapse. Understanding the conditions under which cocaine-associated stimuli take on conditioned reinforcing effects can be used to inform efforts to curtail cocaine use disorder.