Analgesic tolerance and cross-tolerance to i.c.v. endomorphin-1, endomorphin-2, and morphine in mice

The present study examined the development of analgesic tolerance to endomorphin-1 (EM1), endomorphin-2 (EM2), and morphine, and cross-tolerance among these drugs. Male Swiss Webster mice were injected i.c.v. with EM1, EM2, morphine, or vehicle once daily for 5 days, and tested for analgesia in the tail flick test. To determine the extent of cross-tolerance, on the sixth day mice from each of the above groups received i.c.v. injections of EM1, EM2, morphine, or vehicle before analgesic testing. The development of tolerance to EM1 and EM2 closely resembled that of morphine. Complete, symmetrical cross-tolerance was observed between all drugs in the study. These results demonstrate a time-course and extent of tolerance similar to morphine, and support a common mechanism of action through the mu-opioid receptor.