Involvement of the Dopaminergic and Serotonergic Systems in the Antidepressant-like Effect Caused by Ethanolic Extract of Pistacia lentiscus in Tail Suspension Test

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Background: Depression is one of the most common psychiatric disorders worldwide and causes disability. There is a need to produce new agents for the treatment of depression with the maximum efficiency and the lowest side effects. The positive effects of Pistacia lentiscus have been reported in the central nervous system and different disorders. Objectives: This study evaluated the antidepressant-like effect of the ethanolic extract of P. lentiscus (EEPL) in a mouse model and its possible mechanisms. Methods: The male NMRI mice (20 - 25 g) intraperitoneally (i.p.) received vehicle (10 mL/kg), imipramine (30 mg/kg), fluoxetine (20 mg/kg, i.p.), and EEPL (50 - 400 mg/kg). After 45 minutes, the animals were subjected to a tail suspension test (TST). The open-filed test (OFT) was used to assess the animal’s locomotion. To elucidate possible monoaminergic mechanisms, the mice were pre-treated with various receptor antagonists 1 hour before the most effective dose of EEPL. Results: The administration of EEPL (100 - 400 mg/kg) induced an antidepressant-like effect (37.5%, 49.3%, and 63.9% reduction, respectively) in the TST (P < 0.001) without considerable effects on animal locomotion in OFT (P > 0.05). The antidepressant-like effect of EEPL (200 mg/kg) was blocked by the pre-treatment of animals with SCH23390, sulpiride, haloperidol, ketanserin, WAY100135, and p-chlorophenylalanine (pCPA) (P < 0.001), but not with prazosin, yohimbine, or propranolol (P > 0.05). Conclusions: The results show that the antidepressant-like effect of EEPL is mediated by the modulation of dopaminergic and serotonergic systems. Overall, the results suggested that EEPL exerted an antidepressant-like activity in the mouse model of depression, which might be considered a useful drug in the management of depression.