PREVENTION OF MORPHINE DISCONTINUATION PHENOMENON IN MICE BY ONDANSETRON, A SELECTIVE 5-HT3 ANTAGONIST

The effects of ondansetron, a highly potent and selective 5-HT3 recept or antagonist, in the prevention of tolerance to the dependence on mor phine were studied in mice using a 9-day schedule. Chronic administrat ion of morphine (10 mg/kg i.p. twice daily for 9 days) produced tolera nce to the analgesic effects and animals showed withdrawal jumps on da y 10 when challenged with naloxone (2 mg/kg). Chronic treatment with o ndansetron (0.01 and 0.1 mg/kg) followed by saline on days 1-9 failed to produce any significant change in tail-flick latency in the saline- pretreated group. Repeated administration of ondansetron (0.01 and 0.1 mg/kg) for 9 days, however, attenuated the development of tolerance t o the analgesic effect of morphine (10 mg/kg). The higher dose of onda nsetron (0.1 mg/kg) also suppressed the development of morphine depend ence as assessed by naloxone (2 mg/kg)-precipitated withdrawal on day 10 of testing.