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Prevention by the 5‐HT 3 receptor antagonist, ondansetron, of morphine‐dependence and tolerance in the rat
Author(s) -
Hui SiuChun G.,
Sevilla Elenita L.,
Ogle Clive W.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15504.x
Subject(s) - morphine , ondansetron , physical dependence , antagonist , (+) naloxone , receptor antagonist , opiate , pharmacology , conditioned place preference , 5 ht receptor , chemistry , anesthesia , serotonin , medicine , receptor , vomiting
1 The effect of ondansetron, a selective 5‐hydroxytryptamine 3 (5‐HT 3 ) 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 μg 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. 5 5‐Hydroxytryptamine 2 (5‐HT 2 ) receptor antagonism by cyproheptadine (100 or 250 μg kg −1 ; i.p.; 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.