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

ABSTRACT

It has been reported that, the [R]-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 [R]- carbolines is a revesible inhibitory action on MAO-A. These findings suggest that - carbolines, should alleviate at least some of the signs of depression. The purpose of present study is to determine the antidepressant activity of [R]-carbolines harmane, norharmane and harmine. All experiments were carried out on male Swiss-Webster mice [25-30g]. The antidepressant activities of the [R]-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 [o]C. After 30 min of the-carbolines injections, the mice were subjected to forced swimming test for 8 min and their immobility time was recorded. Intraperitoneal [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]. The results suggest that the antidepressant activities of harmane, norharmane and harmine may be mediated through an inverse agonistic mechanism