Background: Previous studies have indicated that administration of saffron extract could induced reward and reduces morphine reward as investigated by place preference and behavioral sensitization in male and female mice. In the present study, the effects of water extract of Crocus sativus on the acquisition and expression of tolerance to morphine-induced hyperalgesia in female N-MRI mice (20-25 g) were investigated. Matherila and Methods: Tail Flick technique was implicated in the present study. Morphine tolerance achived by morphine (50 mg/kg twice daily) injections for three consecutive days. On the 4th day of the experiments, morphine tolerance was assesed in animals by injection of effective dose of morphine (10 mg/kg). The extract of the C. sativus was administered during (development of tolerance) or after induction of morphine tolerance (expression). Results: Results showed that administration of morphine (1, 5, 10 and 20 mg/kg), induced a significant analgesia in animals. Administration of the plant extract (1, 2.5, 5, 10, 50 and 100 mg/kg) also produced analgesia which was statistically significant in dose 10 mg/kg of the extract. Injection of the plant extract (1, 2.5 and 5 mg/kg) in the test day, 30 min before morphine (10 mg/kg) reduced the expression of morphine tolerance. Administration of the extract (1, 2.5 and 5 mg/kg) during the induction of morphine tolerance, have not any effect on the development of morphine tolerance . Conclusion: It could be concluded that injection of the extract of C sativus can inhibit the expression but can not altered the acquisition of morphine tolerance. In addition, the extract could induced analgesia by it-self.

Keywords: Morphine, Crocus sativus, Analgesia, Tolerance

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