Decreased incubation of fentanyl seeking in the absence of proximal drug-paired stimuli

Abstract

Treating substance use disorders is difficult as individuals often resume substance use during abstinence. One potential factor contributing to the recurrence of substance use is incubation of drug craving. Specifically, individuals report higher levels of craving when presented with drug-paired stimuli across abstinence, although this effect is largely absent in opioid-dependent individuals. In preclinical studies, rodents show increased responding on a previously reinforced manipulandum when presented with drug cues, including for opioids. When proximal cues are not presented, self-reported craving tends to decrease across abstinence; however, incubation of drug seeking in the absence of proximal stimuli is rarely tested in animals. As such, we trained male and female Sprague Dawley rats to self-administer the synthetic opioid fentanyl (2.5 μg/kg/infusion) during ten 60-min sessions. Rats were then given three extinction sessions on Days 1, 21, and 30 of withdrawal. Unlike other studies measuring incubation of craving, we did not present drug-paired stimuli (e.g., stimulus lights) during these extinction sessions. Incubation of fentanyl seeking was not observed in the present experiment; instead, responses on the previously drug-paired lever tended to decrease across the three extinction sessions. Based on the results of this experiment, we provide a discussion of some potential interpretational issues associated with the incubation of craving paradigm, including the difficulty in dissociating drug craving from operant sensation seeking (i.e., rodents will respond on a manipulandum to earn access to audiovisual cues that are presented alone). (PsycInfo Database Record (c) 2025 APA, all rights reserved).