Sex differences in effects of predictable and unpredictable footshock on fentanyl self-administration in rats

An operant conditioning paradigm was used to examine effects of predictable and unpredictable footshock on oral fentanyl (50 μg/ml) self- administration (SA) in 12 female and 12 male Wistar rats (Rattus norvegicus). Rats were tested for drug SA under a progressive ratio schedule with and without repeated predictable or unpredictable footshock over 8 weeks. Female rats consumed greater amounts of fentanyl than did male rats. Male rats exhibited greater withdrawal behaviors following naloxone challenge. Predictable footshock with repeated exposure (i.e., chronic stress) was accompanied by greater fentanyl SA than was unpredictable footshock, particularly for female rats. Corticosterone levels were positively correlated with fentanyl SA. Predictability of the stressor also had a greater effect on maintenance of fentanyl SA than it did on relapse to fentanyl SA. Results suggest that sex plays an important role in drug-taking behavior by rats.