Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus

Abstract

A growing body of evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with harmine and imipramine in rats. To this aim, rats were treated for 14 days once a day with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Harmine and imipramine, at all doses tested, reduced immobility time of rats compared with the saline group. Imipramine increased the swimming time at 20 and 30 mg/kg and harmine increased swimming time at all doses. The climbing time increased in rats treated with imipramine (10 and 30 mg/kg) and harmine (5 and 10 mg/kg), without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine and harmine-treated rats by ELISA sandwich assay. Interestingly, chronic administration of harmine at the higher doses (10 and 15 mg/kg), but not imipramine, increased BDNF protein levels in rat hippocampus. Finally, these findings further support the hypothesis that harmine could bring about behavior and molecular effects, similar to antidepressants drugs.

Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

“…To our knowledge, the use of AYA in a controlled clinical setting in patients with current depression --or in any other clinical population --has never been investigated. Moreover, the results of the present study, although preliminary, are corroborated by mounting research showing antidepressive potentials for AYA alkaloids in nonhuman animals [16][17][18][19][20][21][22][23][24] and in humans. 13,25,26 Finally, the reported results may prompt novel research into substances with faster therapeutic actions than currently available pharmacological resources, thus making antidepressive treatment more effective.…”

“…4,5 Studies conducted in rodents by our group and by others using doses of 10-15 mg/kg harmine have demonstrated antidepressive effects for this compound, which were associated with increases in BDNF levels. 17,19,21 Furthermore, harmine, THH, and harmaline are potent natural, selective, reversible, and competitive inhibitors of the MAO enzyme, especially of the MAO-A subtype. 9,36 THH acts as a selective serotonin reuptake inhibitor as well as an MAOI.…”

“…[16][17][18][19][20][21][22][23][24] Furthermore, a double-blind, placebo-controlled animal study reported reduced hopelessness and panic-related signs after acute AYA administration, 25 and preliminary data in humans also support an antidepressive action for AYA. 26 The agonist action of AYA alkaloids on serotonergic receptors and its inhibitory effects on MAO-A, associated with field and laboratory evidence suggesting that AYA causes a sensation of well-being, led to the hypothesis that this substance could be useful in the treatment of depression in humans.…”

A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid “Harmine”

“…Chronic administration of harmine increased brain-derived neurotrophic factor protein levels in rat hippocampus [22] . Effect of harmine on animal behavior was assessed in the forced swimming and open-field tests, and the results showed harmine reduced immobility time and increased both climbing and swimming time of rats, compared to saline group.…”

Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus

“…Different doses of crocin (12.5, 25, and 50 mg/kg) [28,39] were administered intraperitoneally (IP) for 21 days. Neutral and positive control groups received (IP) 1 mL/kg saline and 10 mg/kg imipramine, respectively [40,41]. Crocin and imipramine were dissolved in saline right before injections.…”