Antidepressant-like effect of harmane and other β-carbolines in the mouse forced swim test

Abstract The purpose of the present study was to determine the effects of harmane, norharmane and harmine on the immobility time in the mouse forced swim test (FST) — an animal model of depression. After 30 min of the β-carbolines injections, mice were placed individually in a vertical glass cylinder (height, 25 cm; diameter, 12 cm) containing water about 15 cm deep at 22 ± 1 °C and forced to swim. Treatment of animals with harmane (5–15 mg/kg, i.p.), norharmane (2.5–10 mg/kg, i.p.) and harmine (5–15 mg/kg, i.p.) reduced dose-dependently the time of immobility. Their antidepressant-like effects were not affected by pretreatment with reserpine at the dose of 5 mg/kg, i.p., 18 h before the test, which did not modify the immobility time. Conversely, when flumazenil (5 mg/kg, i.p.) was administered 30 min before the test, it was able to antagonize completely the antidepressant-like effects of harmane, norharmane and harmine. It was concluded that harmane, norharmane and harmine reduce the immobility time in this test, suggesting an antidepressant-like effect, via an inverse-agonistic mechanism located in the benzodiazepine receptors.