Effect of stress on oral morphine and fentanyl self-administration in rats

The effect of immobilization stress (15 min/day) or no stress on oral morphine (0.25-0.5 mg/ml) or fentanyl (5-20 micrograms/ml) self-administration was examined in rats. Animals had access to a morphine or fentanyl solution for 4 days, followed by a single-choice day of access to the opioid solution and a separate water bottle. This 5-day cycle was repeated five times for 7 h/day in home cages. Morphine consumption and preference were assessed for an additional 30 days (i.e., six more cycles) in a subgroup of subjects. Plasma corticosterone levels in the stress groups indicated that the stress manipulation was effective. Over the course of the experiment, animals in the stress groups significantly increased their preference for the opioid solutions during choice days compared to nonstress controls. Morphine preference after 55 days was twice as high in the stress group (70% morphine/30% water) in comparison to controls (34% morphine/66% water). These results indicate that stress increases oral opioid self-administration in rats. Future directions and the implications of this work are discussed.