Effect of stress on oral fentanyl consumption in rats in an operant self-administration paradigm

The effect of intermittent footshock stress (0.8 mA; 0.2 s on; 40 s off on the average; for 10 min/day) on oral fentanyl (50 or 75 μg/ml) self-administration (SA) in operant chambers was examined in male rats. In Experiment 1, after 1 month of initiation of the fentanyl SA by partial water deprivation, animals were tested for lever-pressing for fentanyl (75 μg/ml) under fixed-ratio-4 (FR-4) and progressive-ratio (PR) schedules of reinforcement for 30 min/day in operant chambers. Exposure to footshock stress increased fentanyl SA under the FR-4 and PR schedules compared with a nonstress condition. When water was substituted for the drug, the operant behavior persisted before extinction. In Experiment 2, different rats were tested for lever-pressing for fentanyl (50 μg/ml) under FR-6 and PR schedules. This experiment further assessed the role of taste in the stress-induced fentanyl SA and examined the effect of increasing the schedule requirements (i.e., FR-3, 6, and 12) on lever-pressing for fentanyl. Exposure to footshock stress increased lever-pressing for oral fentanyl SA under the FR schedules of reinforcement. When a quinine solution (30 μg/ml), matched for bitter taste with the fentanyl solution, was substituted for the drug solution, an extinction of the drug-reinforced behavior occureed, indicating that the stress-induced oral fentanyl SA is not related to stress-induced changes in taste sensitivity. In both experiments, no significant stress effects were observed for water consumption in home cage and lever-pressing on the nonoperative lever.