1 The effect of ondansetron, a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist, was studied in morphine-addicted rats. Morphine-dependence and tolerance, induced by drinking increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks, were demonstrated by the naloxone-precipitated withdrawal syndrome and tail flick response to a thermal noxious stimulus (water at 50'C), respectively. 2 Morphine-dependence, assessed by naloxone precipitated withdrawal, was undetectable by the 6th day, when the animals drank only tap water for 7 days after the 3-week induction period. 3 When detoxified rats were offered sucrose and morphine solutions for 10 days, the recurrence of opiate solution preference with relapse to dependence and tolerance was observed. 4 Giving ondansetron (0.1 or 1 Mig kg-1; i.p.; twice daily) on the 14th day of, or 7 days prior to, the 3-week induction period reduced dependence and tolerance seen during the 3-week morphine induction and the 10-day drinking preference periods. twice daily) did not influence morphine-dependence and tolerance. 6 These findings suggest that ondansetron may be useful for treating opiate addiction and lowering the recidivism rate.
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 gLg kg-', i.p. twice daily) 7 days prior to, and during a 21-day period of, morphine availability (increasing concentration from 0.1 to 0.4mgml-') in 5% sucrose solution reduced opiate intake from the 9th day of morphine treatment.3 The administration of ondansetron (0.1 fgkg-', i.p. twice daily) or tropisetron (0.1pg kg-', 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 ug kg-') or ondansetron (1 Lg kg-') 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 pg kg-', 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 ondansetron and tropisetron can reduce morphine intake in both naive and morphine-dependent rats.
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