Conditioned tolerance to morphine hypoalgesia: compensatory hyperalgesia in the experimental group or conditioned...

Five experiments used rats to examine the role of noxious stimulation in the development of contextually controlled morphine hypoalgesic tolerance and in the mediation of this tolerance by an associated hyperalgesic response. There was evidence for contextually controlled tolerance to morphine's hypoalgesic effects and an associated hyperalgesic response in rats injected with morphine and trained with noxious stimulation, but not in rats repeatedly exposed to morphine in the absence of that stimulation (Experiments 1 and 5). Latent inhibition (Experiment 2) and extinction (Experiment 3) of tolerance also depended upon pairing drug-related cues with noxious stimulation. The level of sensitivity-reactivity to noxious stimulation in morphine-tolerant rats tested with the drug was related to the intensity of the noxious stimulation that had been paired with the test context (Experiment 4). The results were interpreted to mean that some of the evidence for a Pavlovian involvement in tolerance development can be explained in terms of morphine's interference with the acquisition, but not with the expression of the hypoalgesic response otherwise acquired by cues paired with noxious stimulation.