Context-specific morphine tolerance on the paw-pressure and tail-shock vocalization tests: evidence of associative tolerance without conditioned compensatory responding.

Abstract

Demonstrations of associative tolerance to the analgesic effects of morphine, not confounded by practice or novelty effects, have been restricted to the tail-flick and flinch-jump tests. Experiment 1 investigated whether associative tolerance would be found on two other nociceptive assessment methods: the paw-pressure withdrawal and tail-shock vocalization thresholds. Experiment 2 tested the hypothesis that conditioned compensatory behavioral responses are the substrate of associative morphine tolerance in the paw-pressure, tail-shock, and tail-flick tests. Rats were given eight morphine injections (20 mg/kg, i.p.) explicitly paired or unpaired with a distinctive context. Control animals were given saline injections over the course of conditioning. Animals were then tested after morphine (experiment 1) or placebo injections (experiment 2) in the context. There was evidence of context-specific tolerance across both testing methods, with a rightward shift of dose-response curves of paired relative to unpaired animals. No evidence of conditioned compensatory responding was found on any of the three testing methods. The data indicated that, although Pavlovian processes can play a major role in tolerance acquisition, there was little support for the thesis that the conditioned tolerance response is a behavioral effect that is opposite in direction to the direct effects of the drug.