CROSSTOLERANCE BETWEEN BUTORPHANOL AND MORPHINE IN RATS

To investigate the antinociceptive effects of morphine and U-50,488 af ter continuous administration with butorphanol, rats were intracerebro ventricularly (ICV) infused with butorphanol (26 nmol/mu l/h) through osmotic minipumps for 3 days. Six hours after termination of infusion, the rats were challenged with different doses of morphine or U-50,488 . Antinociceptive effects, as assessed by tail-flick and acetic acid w rithing tests, were measured 15 min after challenge. Development of cr osstolerance to morphine was evident in butorphanol-infused animals. T he study also revealed that crosstolerance to butorphanol developed in continuously ICV morphine-infused animals. Continuous ICV infusion wi th butorphanol produced a marked rightward shift of the antinociceptiv e dose-response curve resulting from U-50,488 challenge. These results showed that there is an antinociceptive crosstolerance between butorp hanol and morphine, and crosstolerance to U-50,488 developed in contin uously butorphanol-infused animals. The present data suggested that ch ronic ICV treatment with high doses of butorphanol can lead to desensi tization of the antinociceptive systems mediated through the central k appa as well as mu receptors in rats.