Introduction: Depression has multifactorial characters including brain-behavioral disorders, alteration in cognitive psychomotor and emotional process. Millions of people are worldwide suffering from this illness. This disease happens in all ages of men and women. This research tries to introduce a traditional medication in comparison with common chemical anti-depressant drugs. This experiment was designed to evaluate probably the antidepressant effect of Citrullus colocynthis fruit extraction.

Materials and methods: Thirty-two male mice (Balb/c) was randomly divided to four groups (n=8 each). Animals adapted and treated to diazepam, imipramine, aqueous and hydro alcoholic extract of Citrullus colocynthis fruit. All administrations were done via intraperitoneal 0.2ml/animal. Plant material after grinding was extracted with ethanol and evaporated under reduced pressure. Tail suspension test was carried out to assay the antidepressant effect of plant extraction in animals. The test was carried on before, and as well as 30, 60 and 120 minutes after injections.

Results: Our data indicated that after intraperitoneal administration of aqueous and ethanol extract, immobility duration exhibits statistically significant increase compared to agitation phase in all times after injection(P<0.05). Ethanol extract reduced statistically agitation time in 30, 60 and 120 min after injection compared to imipramine. Both aqueous and ethanol extract elevated immobility in minute 60(P<0.5).

Conclusion: The present study suggested that Citrullus colocynthis extract could possess potential antidepressant and sedative effects which would be of therapeutic interest for using in the treatment of patients with depressive disorders. We suggest more research in this regard.