Temporal factors in the effect of restraint stress on morphine-induced behavioral sensitization in the rat

The role of associative factors in the effect of 15 min/day of restraint stress on morphine-induced behavioral sensitization was examined. Male rats were initially given seven systemic (10 mg/kg, IP) or intraventral tegmental area (VTA, 5 micrograms/side) [corrected] injections of morphine, and were exposed to restraint, either just prior to drug injection (Paired-Stress) or 24 h after injection (Unpaired-Stress), or to no restraint (Control). In subsequent tests for behavioral sensitization to low doses of morphine (0.75 or 3.0 mg/kg, IP), animals in the Paired-Stress condition were more active than animals in the Unpaired-Stress or Control conditions. These results indicate that temporal and possibly associative factors may contribute to stress-induced changes in sensitization to the behavioral activating effects of opioids.