Test-specific manifestations of associative tolerance to the analgesic effects of morphine in the rat

The acquisition of associative tolerance to the analgesic effects of morphine as assessed on the hotplate test was investigated in two experiments. Associative contingencies were manipulated by giving rats eight moderately high morphine doses (20 mg/kg) either paired or unpaired with a distinctive context at a 96-h interdose interval. Tolerance was evaluated as shifts in dose-response curves of morphine-experienced relative to morphine- naive animals tested in the distinctive context. Experiment 1, in which independent groups of animals were tested with hot-plate temperatures of 50°C (N = 302) and 54°C (N = 175), produced no evidence of context-specific tolerance to morphine. Experiment 2 (N = 200) evaluated the effect of contextual contingencies of drug delivery on the development of morphine tolerance in animals tested on either the hot-plate or the tailflick test. As found in Experiment 1, animals tested on the hot plate showed no context- specific tolerance, whereas animals tested on the tailflick displayed pronounced associative-tolerance effects. The data suggest that the hot plate, as opposed to other tests of analgesia, does not provide a sensitive measure of associative morphine tolerance.