Harmine produces antidepressant-like effects via restoration of astrocytic functions.
Fengguo Liu, Jingjing Wu, Yu Gong, Peng Wang, Lei Zhu, Lijuan Tong, Xiangfan Chen, Yong Ling, Chao Huang
Progress in Neuro-Psychopharmacology and Biological Psychiatry October 3, 2017 DOI: 10.1016/j.pnpbp.2017.06.012 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Mice exposed to chronic unpredictable stress |
| Interventions | Harmine l-Alpha-Aminoadipic Acid (L-AAA) |
| Dose | 10, 20 mg/kg harmine |
| Measures | tail suspension test (TST), forced swimming test (FST), sucrose preference test |
| Topics | Depression |
| Keywords | Astrocyte Chronic unpredictable stress Glutamate transporter 1 Harmine |
| Key findings | Harmine reduced depression-like behaviors in chronically stressed mice and prevented stress-induced reductions in BDNF, hippocampal neurogenesis, GLT-1, and GFAP. Because the astrocyte-killing agent L-AAA weakened these effects, the authors conclude that harmine's antidepressant-like action likely works through restoring astrocytic function, supporting the view that astrocytic dysfunction contributes to depression. |
Abstract
Depression is a world-wide disease with no effective therapeutic methods. Increasing evidence indicates that astrocytic pathology contributes to the formation of depression. In this study, we investigated the effects of harmine, a natural β-carboline alkaloid and potent hallucinogen, known to modulate astrocytic glutamate transporters, on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. Results showed that harmine treatment (10, 20mg/kg) protected the mice against the CUS-induced increases in the immobile time in the tail suspension test (TST) and forced swimming test (FST), and also reversed the reduction in sucrose intake in the sucrose preference experiment. Harmine treatment (20mg/kg) prevented the reductions in brain-derived neurotrophic factor (BDNF) protein levels and hippocampal neurogenesis induced by CUS. In addition, harmine treatment (20mg/kg) increased the protein expression levels of glutamate transporter 1 (GLT-1) and prevented the CUS-induced decreases in glial fibrillary acidic protein (GFAP) protein expressions in the prefrontal cortex and hippocampus, suggesting that restoration of astrocytic functions may be a potential mechanism underlying the antidepressant-like effects of harmine. This opinion was proved by the results that administration of mice with l-Alpha-Aminoadipic Acid (L-AAA), a gliotoxin specific for astrocytes, attenuated the antidepressant-like effects of harmine, and prevented the improvement effects of harmine on BDNF protein levels and hippocampal neurogenesis. These results provide further evidence to confirm that astrocytic dysfunction contributes critically to the development of depression and that harmine exerts antidepressant-like effects likely through restoration of astrocytic functions.
Comparable studies
Other preclinical and animal studies on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... | 2011 | Animal experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study |
Citations in the library
Cited by 16
- Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents Biomedicines February 5, 2023
- Ayahuasca: A review of historical, pharmacological, and therapeutic aspects. Psychiatry and Clinical Neurosciences Reports December 1, 2023
- Effects of psychedelics on neurogenesis and broader neuroplasticity: a systematic review. Mol Med December 19, 2024
- Ayahuasca and Dimethyltryptamine Adverse Events and Toxicity Analysis: A Systematic Thematic Review. International journal of toxicology 2024
- Ayahuasca and its major component harmine promote antinociceptive effects in mouse models of acute and chronic pain. Journal of Ethnopharmacology April 6, 2024
and 11 more in the library
Cites 5
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report Brazilian Journal of Psychiatry March 1, 2015
- Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression Journal of Clinical Psychopharmacology December 11, 2015
- Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): a systematic review of clinical trials published in the last 25 years Therapeutic Advances in Psychopharmacology March 18, 2016
- Ketamine for treatment-resistant depression: recent developments and clinical applications. Evidence-Based Mental Health May 2016