Conditioned morphine tolerance in the rat: Absence of a compensatory response and cross-tolerance with stress

In 4 experiments with 193 male Holtzman rats, evidence was obtained that tolerance development to morphine analgesia occurred most rapidly when morphine delivery was paired with salient contextual cues. Contextual cues previously paired with morphine did not elicit conditioned drug-compensatory responses when presented to nondrugged Ss. These results were obtained by different analgesia assessments, with different drug-administration analgesia-test latencies, and in environments differing with respect to stress level. Stress level influenced nociceptive response, as it was found that the combination of bright illumination, white noise, and a strong odor resulted in antinociception in the absence of drug. Ss that had a history of receiving morphine in this stressful context were tolerant to this stress-induced antinociception but only when morphine was present in their systems. In the final 2 studies, this antinociception, which was cross-tolerant with morphine, was characterized with respect to naloxone reversibility and brain levels of met- and leu-enkephalin as determined by radioimmunoassay. (87 ref)