Absence of environment-specificity in morphine tolerance acquired in non-distinctive environments: habituation or stimulus overshadowing?

The experiments reported here investigated the mechanisms of drug tolerance acquisition in environments differing in distinctiveness. Specifically, they examined the hypothesis that tolerance acquired in non-distinctive environments might involve habituation while tolerance acquired in distinctive environments involves a classical conditioning or associative learning mechanism. In Experiment 1, rats pre-exposed to injection-ritual cues (placebo injections) prior to acquisition of tolerance to morphine analgesia in distinctive or non-distinctive environments showed a typically attenuated tolerance response on an environment-change test. The magnitude of the attenuation was not affected by the distinctiveness of the acquisition environment. In Experiment 2, rats acquiring tolerance in distinctive or non-distinctive environments, but without prior injection-ritual pre-exposure, did not demonstrate an attenuation of tolerance on an environment-change test. Tolerance acquired in either environment was unaffected by a subsequent rest period in the colony room, but was attenuated by a subsequent period of daily placebo injections in the colony room. It is argued that failure to observe environment-specific tolerance, as in Experiment 2 and in previous reports in the literature, may reflect overshadowing of environmental stimuli by injection-ritual stimuli, and are not indicative of a fundamental difference between the mechanisms of tolerance acquisition in environments varying in distinctiveness.