Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 33; no. 8; pp. 1425 - 1430
• Main Authors: Fortunato, Jucélia J., Réus, Gislaine Z., Kirsch, Tamires R., Stringari, Roberto B., Stertz, Laura, Kapczinski, Flávio, Pinto, Joel P., Hallak, Jaime E., Zuardi, Antônio W., Crippa, José A., Quevedo, João
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 13.11.2009; Elsevier
• Subjects: Adult and adolescent clinical studies; Analysis of Variance; Animals; Antidepressive Agents - pharmacology; BDNF; Biological and medical sciences; Brain-Derived Neurotrophic Factor - metabolism; Depression; Depression - drug therapy; Depression - pathology; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay - methods; Forced swimming test; Harmine; Harmine - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Imipramine; Imipramine - pharmacology; Male; Medical sciences; Mood disorders; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Swimming - psychology; Forced swimming test; Imipramine; MAO-A; BDNF; Depression; CDK; MDD; Harmine; 5-HT2A; Rat; Psychotropic; Central nervous system; Reuptake inhibitor; Encephalon; Antidepressant agent; Brain derived neurotrophic factor; Mood disorder; Serotonin; Acute; Rodentia; Catecholamine; Tricyclic compound; Stress; Vertebrata; Mammalia; Animal; Neurotransmitter; Norepinephrine; Hippocampus
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2009.07.021

Harmine is a β-carboline alkaloid that inhibits monoamine reuptake systems. Findings point to an antidepressant effect of the compounds that increases the levels of monoamines after monoamine oxidase inhibition. The present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of harmine and imipramine in rats. To this aim, rats were acutely treated with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavior was assessed in the forced swimming and open-field tests. Afterwards, hippocampal BDNF protein levels were assessed in imipramine- and harmine-treated rats by ELISA-sandwich assay. We observed that harmine at doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time, and increased both climbing and swimming time of rats compared to saline group, without affecting locomotor activity. Acute administration of harmine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. Finally, these findings further support the hypothesis that harmine could be a new pharmacological target for the treatment of mood disorders.