Evidence for a role of conditioning in the development of tolerance to morphine-induced inhibition of gastrointestinal transit in rats

Groups of rats were administered s.c. saline or morphine for 14 consecutive days and received morphine, saline or no treatment on day 15. Significant and consistent environmental cues were established through the treatment and test periods. Transit of a charcoal meal along the gastrointestinal tract, measured on day 15, was significantly greater in rats conditioned to daily morphine, followed by saline on day 15, than in any other group. This enhanced transit was approximately equal in magnitude to the amount of developed tolerance to morphine. These results support the hypothesis that tolerance to opiates may be partly explained by a compensatory conditioned physiological response opposing the acute effect.