Morphine tolerance acquisition as an associative process.

The results of several experiments supported the proposal that morphine analgesic tolerance is a manifestation of an association between the drug administration ritual and the systemic effects of the drug: (a) Presenting environmental cues previously associated with morphine, but without the drug, attenuated established tolerance (i.e., morphine tolerance can be extinguished), (b) repeated presentations of the morphine administration procedure, prior to its pairing with the opiate, retarded the acquisition of tolerance (i.e., morphine tolerance is subject to "latent inhibition"), and (c) placebo sessions interspersed between morphine sessions deleteriously affected the development of tolerance (i.e., morphine tolerance is subject to the decremental effects of partial reinforcement). These findings appear inexplicable by most traditional theories of tolerance, which do not emphasize the role of drug-associated environmental cues in the development of tolerance. Additionally, it is suggested that the conditioning analysis of tolerance is congenial with a current view of habituation, and there may be a similar associative basis for the response decrement to both endogenous and exogenous iterative stimulation.