Background.: Crocus sativus stigmata known by more famous name saffron is an ancient spice which is used both in Persian cuisine and Islamic traditional medicine. There is a lot of pharmacological activities reported from saffron including anti-tumor activity, anti-nociception and anti-inflammatory properties, having radical scavenger compounds, anti-depressive, anti-convulsant, having inhibitory effect on beta amyloid aggregation, reducing the ischemia induced oxidative damage, etc.In current study the effect of ethanolic extract of saffron and fluoxetine alongside each other in behavioral models of depression and in expression of Serotonin and norepinephrine transporters evaluated.

Materials and Methods:  Male albino mice weighing 25-30 g were used.Crocus sativus stigmata (Saffron). Petals crushed and mixture of ethyl alcohol 80% in Distilled water used as extraction solvent. 2 grams of crushed petals extracted triple time with maceration method Each of interventions performed intraperitoneally at 10 AM for 21 consecutive days and behavioral test done on day 22..The animals studied for depression behavior by Tail suspension test and forced swimming test and Elevated plus maze and After behavioral tests animals euthanized using cervical dislocation. Brain extracted and fixed in formalin 10% then paraffin blocks made. Sagittal 40 µm sections were cut using Leica essential microtome  from frontal lobes then paraffin embedded samples deparaffinized and hydrated in alcohol series and the samples went for Immunohistochemistry for SERT and NET expressions.

Results: The resulted measurements in TST, FST and EPM test have shown that average immobility time slightly decreased through all the interventions even though this difference were most significant when extract administered along the fixed dose of fluoxetine. The average immobility time decreased significantly from 238±16.3 seconds in Ctrl group to 172±29.5 and 149±30 seconds for Ext50+Flu and Ext100+Flu, Respectively. TST immobility time also decreased significantly to 172±26.4 seconds in fluoxetine only administration as Control positive group. Result of tissue SERT expression showed that among the experiment groups, Ext50+Flu, Ext100+Flu and Flu had highest amount of SERT expression significantly comparing to the Ctrl Group. As of Tissue Expression of NET showed that there was significant different between Ext100+Flu and Flu groups comparing to the Ctrl group.

Conclusion: In current study. It has been shown, crocus sativa stigma extract alongside Fluoxetine has anti depression effect and As the results indicate treatment with the extract in both concentrations alongside fluoxetine and fluoxetine alone induced expression of SERT while the extraction in concentration 100 mg.kg-1 alongside fluoxetine induced NET expression more comparing to the control groups. Some mechanism of actions is proposed for antidepressant effect of crocus sativa such as having serotonergic, anti-inflammatory, anti-oxidant, neuroprotective and having Hypothalamus-pituitary-adrenal axis modulating effects. On the other hand, changes in neurotransmission like expression of reuptake transporters believed to be related with long lasting effects of antidepressant agents.

Ramin Ataee is a researcher at the Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran, with expertise in pharmaceutical sciences and medical research.