5-HT3 antagonists reduce morphine self-administration in rats.

1. The effects of the 5-HT3 receptor antagonists, ondansetron and tropisetron, on morphine consumption were studied in naive and morphine-dependent rats. 2. The administration of ondansetron (1 microgram kg-1, i.p. twice daily) 7 days prior to, and during a 21-day period of, morphine availability (increasing concentration from 0.1 to 0.4 mg ml-1) in 5% sucrose solution reduced opiate intake from the 9th day of morphine treatment. 3. The administration of ondansetron (0.1 microgram kg-1, i.p. twice daily) or tropisetron (0.1 microgram kg-1, i.p. twice daily) on the 14th day of the 21-day period of morphine treatment failed to reduce opiate consumption. Administration of the larger doses of tropisetron (1 microgram kg-1) or ondansetron (1 microgram kg-1) reduced morphine consumption. 4. After receiving 21 days of treatment with morphine alone or with the ondansetron or tropisetron regimens identified above, the sucrose solutions were substituted with tap water for 7 days. These detoxified rats were then allowed a free choice of sucrose or morphine for 10 days. Animals that had received concomitant treatment with ondansetron or tropisetron showed reduced morphine intake when compared with the controls treated with morphine only or with vehicle-treated controls. 5. The administration of cyproheptadine (100 or 250 micrograms kg-1, i.p. twice daily) on the 14th day of 21-day morphine treatment failed to modify morphine intake and also failed to influence the subsequent intake of the opiate in the free choice situation. 6. It is concluded that ondasetron and tropisetron can reduce morphine intake in both naive and morphine-dependent rats.