Saffron (Crocus sativus L.) stigma reduces symptoms of morphine-induced dependence and spontaneous withdrawal in rats

Background: Chronic morphine induces physical and psychological dependence signs. Saffron (Crocus sativus L.) stigma has been shown to have anxiolytic, antidepressant, and antinociceptive properties and to alleviate naloxone-precipitated withdrawal signs. Objectives: Therefore, this study was designed to examine the effects of saffron aqueous extract on the severity of physical-psychological dependence, voluntary morphine consumption, and the cerebrospinal fluid (CSF) serotonin levels following locomotor sensitization in morphine-dependent rats and in rats undergoing morphine withdrawal. Materials: Adult male rats were treated with morphine (10 mg/kg, sc twice daily) for 10 days. Rats received saffron extract (60 mg/kg, ip) daily, during the induction of morphine dependence and/or withdrawal. Then, rats were tested for spontaneous withdrawal signs, anxiety using the elevated plus-maze, depression using sucrose preference test, and voluntary morphine consumption using a two-bottle choice paradigm, and then challenged with morphine (1 mg/kg, ip) to evaluate of locomotor sensitization and CSF serotonin levels. Results: The results showed saffron extract during induction of morphine dependence decreased the severity of withdrawal signs (P = .05), while it had no effect on anxiety and depression-like behaviors. Saffron extract during morphine withdrawal exhibited an increase in the percentage (or ratio) of open/total arm entries (P = .017), higher levels of sucrose preference (P = .0001), a lower morphine preference ratio (P = .02) and also, a decrease in locomotor activity (P = .004) and an increase in the CSF serotonin levels (P = .041) in rats challenged to morphine. Conclusions: Saffron extract may exert a protective effect against morphine-induced behavioral sensitization in rats, probably through increasing serotonin levels.