title: Antidepressant-like effect of harmane and other beta-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 beta-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 degrees 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.
authors.affiliation: Department of Pharmacology, School of Medicine, Mazandaran University of Medical Sciences, Sari 48168, Iran. davoodfarzin@yahoo.com
authors.forename: Davood
authors.initials: D
authors.lastname: Farzin
authors.forename: Nazanin
authors.initials: N
authors.lastname: Mansouri
mesh_terms: D000818:Animals; D000928:Antidepressive Agents; D001522:Behavior, Animal / Q000187:drug effects; D002243:Carbolines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology; D013550:Swimming / Q000523:psychology*; D013565:Sympatholytics / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D002243:Carbolines; D018757:GABA Modulators; D008996:Monoamine Oxidase Inhibitors; D013565:Sympatholytics; D005442:Flumazenil; D006247:Harmine; C005010:harman; D012110:Reserpine; C010262:norharman