5-HT(3) ANTAGONISTS REDUCE MORPHINE SELF-ADMINISTRATION IN RATS

1 The effects of the 5-HT3 receptor antagonists, ondansetron and tropi setron, on morphine consumption were studied in naive and morphine-dep endent rats. 2 The administration of ondansetron (1 mug kg-1, i.p. twi ce daily) 7 days prior to, and during a 21-day period of, morphine ava ilability (increasing concentration from 0.1 to 0.4 mg ml-1) in 5% suc rose solution reduced opiate intake from the 9th day of morphine treat ment. 3 The administration of ondansetron (0.1 mug kg-1, i.p. twice da ily) or tropisetron (0.1 mug kg-1, i.p. twice daily) on the 14th day o f the 21-day period of morphine treatment failed to reduce opiate cons umption. Administration of the larger doses of tropisetron (I mug kg-1 ) or ondansetron (1 mug kg-1) reduced morphine consumption. 4 After re ceiving 21 days of treatment with morphine alone or with the ondansetr on or tropisetron regimens identified above, the sucrose solutions wer e substituted with tap water for 7 days. These detoxified rats were th en allowed a free choice of sucrose or morphine for 10 days. Animals t hat had received concomitant treatment with ondansetron or tropisetron showed reduced morphine intake when compared with the controls treate d with morphine only or with vehicle-treated controls. 5 The administr ation of cyproheptadine (100 or 250 mug kg-1, i.p. twice daily) on the 14th day of 21-day morphine treatment failed to modify morphine intak e and also failed to influence the subsequent intake of the opiate in the free choice situation. 6 It is concluded that ondansetron and trop isetron can reduce morphine intake in both naive and morphine-dependen t rats.