Discriminative stimulus properties of fentanyl and morphine: tolerance and dependence

Using a food-reinforced two-lever operant procedure, rats were trained to discriminate 0.04 mg/kg fentanyl from saline. At different time intervals after the establishment of discriminative responding, stimulus generalization experiments were performed with equivalent dose ranges of fentanyl (0.0025 to 0.02 mg/kg) and morphine (2.5 to 20 mg/kg). It was found that the ED50 values of both compounds for generalization with the narcotic discriminative stimulus complex, did not change over a 4-month period. The subjects used in this study demonstrated marked tolerance to narcotic analgesia, but none of them showed signs reminescent of narcotic dependence. It is concluded that the discriminative stimulus properties of narcotic analgesics are not subject to tolerance.