Development of context-specific tolerance to morphine: Support for a dual-process interpretation.

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Abstract
Four experiments were concerned with the de\elopment in rats of context-specific tolerance to the sedating and analgesic effects of" morphine. Experiment I was conducted to assess the temporal course of act is ity changes and analgesia consequent to acute morphine administration. Experiments 2. 3, and 4 were conducted to assess the development of context-specific morphine tolerance in the two measures under different conditions of pairing of morphine with a distinctive environment. In support of a dual-process model (postulating both a general tendency for conditioned diminution of unconditioned responding and a more restricted influence of the development of specific conditioned compensators responses), tolerance was observed in both measures, but evidence of conditioned compensatory response was found only in the activity measure. The differential evidence of conditioned compensator) response in the two measures was interpreted as consistent with the fact that the activity measure showed a biphasic uncondi- tioned response in Experiment I whereas the analgesic measure did not. The tolerance that a subject develops to certain drugs with repeated experience is. at least in pan, an associative conse- quence (Siegel. 1975. 1977). The experiments reported here are concerned svith elucidating the kind of associative proc- esses that may be involved in morphine tolerance and ssith evaluating the potential usefulness of a recent proposal of Wagner (1981) as to the circumstances under which "condi- tioned compensatory responses," antagonistic to the promi- nent unconditioned response (Siegel, 1981), mas be impli- cated.

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