Tolerance to morphine-produced discriminative stimuli and analgesia.

Male hooded rats were trained in Skinner boxes to press one lever after a morphine injection (10 mg/kg) and another lever after a saline injection (1 ml/kg) on an FR 10 schedule of food reinforcement. After the drug discrimination was well established, the rats were tested for stimulus generalization at different doses of morphine, followed by assessment of tail withdrawal latency as a measure of analgesia. Subjects were then administered increasing doses of morphine sulphate to induce an increased level of tolerance. New dose-response curves indicated that tolerance developed to the morphine-induced discriminative stimulus, and to the analgesic action of morphine, but doses of morphine that failed to cause detectable analgesia still produced a pronounced discriminative stimulus.