مقايسه اثرات ضدافسردگي هارمان ، نورهارمان و هارمين در موش آزمايشگاهي

Evaluation of antidepressant activities of harmane, norharman and harmine in mice

Background&Objective: It has been reported that, the Beta-carboline alkaloids of peganum harmala seeds have a stimulatory action on serotonin and catecholamines releases in different brain regions. In addition, one of the most important pharmacological effects demonstrated for Beta-carbolmes is a revesible inhibitory action on MAO-A. These findings suggest that Beta-carbolines, should alleviate at least some of the signs of depression. The purpose of present study is to determine the antidepressant activity of Beta-carbolines harmane, norhannane and harmine. Materials&Methods: All experiments were carried out on male Swiss-Webster mice (25-30g). The antidepressant activities of the Beta-carbolines were assessed using the forced swim test. This test is the most widely used tool for antidepressant activity preclinically. In this test, mice were placed into a cylinderical glass (25 cm height, 12 cm in diameter) containing a column of 15 cm of water at 25 +1 °C. After 30 min of the Beta-carbolines injections, the mice were subjected to forced swimming test for 8 min and their immobility time was recorded. Results: Intrperitoneal (i.p.) injections of harmane (5-15 mg/kg), norharmane (2.5-10 mg/kg) and harmine (5-15 mg/kg) significantly decreased the immobility time in the mouse forced swim test. The inhibitory effects of harmane, norharmane and harmine were antagonized by flumazenil (5 mg/kg, i.p.) but not by reserpine (5 mg/kg, i.p., 18 h before test). Conclusion: The results suggest that the antidepressant activities of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism.