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

ABSTRACT

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.

KEYWORDS:

• Morphine
• saffron
• anxiety
• depression
• morphine preference
• locomotor sensitization
• serotonin

Abbreviation

CSF	=	Cerebrospinal fluid
EPM	=	Elevated plus-maze
SPT	=	Sucrose preference test
CPP	=	Conditioned place preference
TBC	=	Two-bottle choice
HPLC	=	High-performance liquid chromatography
ANOVA	=	Analyses of variance
BDNF	=	Brain-derived neurotrophic factor

Acknowledgements

This work was supported by the grants from Semnan Medical Sciences Universities (Semnan, Iran, 883). This article is part of the thesis of Mr. Benyamin Kiashemshaki for the degree of Master of Sciences in Physiology.

Disclosure of interest statement

The authors declare that they have no conflict of interest.