Effects of β-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: Further evidence of antidepressant properties

Fortunato, Jucélia Jeremias; Réus, Gislaine Z.; Kirsch, Tamires R.; Stringari, Roberto B.; Fries, Gabriel R.; Kapczinski, Flávio; Hallak, Jaime E. C.; Zuardi, Antônio Waldo; Crippa, José Alexandre de Souza; Quevedo, João

doi:10.1016/j.brainresbull.2009.09.008

Cited by 95 publications

(76 citation statements)

References 51 publications

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“…Harmine has a wide spectrum of pharmacological properties, including antidepressant effects, 11,12) and several psychiatric conditions including depression are closely associated with the circadian clock. 14) We previously reported that harmine dose-dependently lengthens the circadian period in NIH 3T3 cells.…”

Section: Discussionmentioning

confidence: 99%

“…9) Harmine is also found in common plant-derived foods and animal tissues, 10) and it has antiplasmodial, antioxidative, antimutagenic and antigenotoxic activities, as well as antidepressant properties. [11][12][13] Several psychiatric conditions, including depression, are closely associated with the circadian clock. 14) Although we previously reported that harmine dose-dependently lengthens the circadian period of Bmal1 expression in NIH 3T3 cells, 15) the effects of harmine on the master clock in the SCN remain unknown.…”

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confidence: 99%

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Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

Kondoh

Yamamoto

Tomita

et al. 2014

Biological & Pharmaceutical Bulletin

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The circadian clock is a cell-autonomous endogenous system that generates circadian rhythms in the behavior and physiology of most organisms. We previously reported that the harmala alkaloid, harmine, lengthens the circadian period of Bmal1 transcription in NIH 3T3 fibroblasts. Clock protein dynamics were examined using real-time reporter assays of PER2::LUC to determine the effects of harmine on the central Key words carboline alkaloid; circadian clock; PER2::LUC protein; real-time reporter assay; suprachiasmatic nucleus The circadian clock is an endogenous cell-autonomous system that generates circadian rhythms in the behavior and physiology of most organisms. The master clock in mammals is located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus, 1,2) which controls most aspects of physiology such as sleep-wake cycles, body temperature, hormone secretion, blood pressure and metabolism.3,4) The circadian clock mechanism consists of a network of autoregulatory transcription-based feedback loops that drive the rhythmic expression of clock genes such as Per1, Per2 and Bmal1, 5) and these cell-autonomous and self-sustained oscillators are found not only in the SCN but also in peripheral tissues as well as dissociated cells. Acute induction of the mRNA expression of clock genes plays a critical role in phase shifting the circadian clock both in cells cultured in vitro and in vivo. In addition to transcriptional feedback regulations, some essential roles of post-translational modifications such as phosphorylation and ubiquitination have been reported. [6][7][8] The harmala alkaloid, harmine, is a β-carboline alkaloid that was originally isolated from seeds of Peganum harmala and Banisteropsis caapi, both of which have traditionally been used in ritual and medicinal preparations of the Middle East, Central Asia and South America. 9) Harmine is also found in common plant-derived foods and animal tissues, 10) and it has antiplasmodial, antioxidative, antimutagenic and antigenotoxic activities, as well as antidepressant properties.11-13) Several psychiatric conditions, including depression, are closely associated with the circadian clock.14) Although we previously reported that harmine dose-dependently lengthens the circadian period of Bmal1 expression in NIH 3T3 cells, 15) the effects of harmine on the master clock in the SCN remain unknown. We therefore evaluated clock protein dynamics in neuronal cells and in SCN slices by monitoring PER2::LUC bioluminescence in real-time to determine the effects of harmine on the master clock in the SCN.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

Kondoh

Yamamoto

Tomita

et al. 2014

Biological & Pharmaceutical Bulletin

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Osório

Sanches

Macedo

et al. 2015

Rev. Bras. Psiquiatr.

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389

311

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Objectives: Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Å sberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

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“…11 However, the opposite results -i.e., an increase in BDNF levels in stressed animals -have been reported by other authors, suggesting the existence of a compensatory mechanism in response to stress. 7 It is important to note that many of the changes found in animals exposed to stress procedures and that serve as criteria for face validation (such as anhedonia) and for construct validation (such as changes in the HPA axis and in neurotrophin levels) are reversed by various classes of clinically effective antidepressants (e.g., fluoxetine and imipramine), 12 demonstrating the predictive validity of this animal model. However, the CMS model has two major drawbacks.…”

Section: Chronic Mild Stressmentioning

confidence: 92%

“…Usually, animals subjected to a stress protocol exhibit increased levels of corticosterone and an increase in adrenal gland weight. 7 Changes in lipids and proteins, as well as decreases in the activity of antioxidant enzymes and increases in pro-inflammatory cytokines, were observed in animals subjected to these experimental protocols. 8,9 In recent years, many researchers have focused on the importance of neurotrophins, which are involved in cellular plasticity.…”

Section: Chronic Mild Stressmentioning

confidence: 96%

Animal models as tools to study the pathophysiology of depression

Abelaira

Réus

Quevedo

2013

Rev. Bras. Psiquiatr.

199

116

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The incidence of depressive illness is high worldwide, and the inadequacy of currently available drug treatments contributes to the significant health burden associated with depression. A basic understanding of the underlying disease processes in depression is lacking; therefore, recreating the disease in animal models is not possible. Popular current models of depression creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology. Within this context, this study aims to evaluate animal models of depression and determine which has the best face, construct, and predictive validity. These models differ in the degree to which they produce features that resemble a depressive-like state, and models that include stress exposure are widely used. Paradigms that employ acute or sub-chronic stress exposure include learned helplessness, the forced swimming test, the tail suspension test, maternal deprivation, chronic mild stress, and sleep deprivation, to name but a few, all of which employ relatively short-term exposure to inescapable or uncontrollable stress and can reliably detect antidepressant drug response.

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Effects of β-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: Further evidence of antidepressant properties

Cited by 95 publications

References 51 publications

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

Harmine Lengthens Circadian Period of the Mammalian Molecular Clock in the Suprachiasmatic Nucleus

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

Animal models as tools to study the pathophysiology of depression

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