Harmaline Attenuates Stress-Induced Depression-Like Behaviour and Biochemical Alterations in Mice
Khush Jain, Fariah Rizwani, Nisarg Sawant, Adnan Rayeen, Sainyukta Patil, Prashant Patole
preprint DOI: 10.21203/rs.3.rs-8342564/v1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study |
|---|---|
| Population | Mice |
| Interventions | Harmaline Imipramine |
| Dose | 15 mg/kg harmaline, 30 mg/kg imipramine |
| Duration | 21 days |
| Topics | Depression |
| Key points | Harmaline (15 mg/kg) for 21 days reversed depression-like behaviors in mice exposed to chronic unpredictable mild stress, with effects comparable to imipramine. |
Abstract
Abstract Depression is a debilitating psychiatric disorder affecting millions worldwide. The Chronic Unpredictable Mild Stress (CUMS) model is widely used to simulate depression-related behavioural and neurobiological changes in rodents. This study evaluated the antidepressant-like effects of harmaline, a monoamine oxidase (MAO) inhibitor derived from Peganum harmala , in comparison to imipramine, a standard antidepressant. Mice exposed to CUMS received daily oral doses of harmaline (15 mg/kg) or imipramine (30 mg/kg) for 21 days. Harmaline significantly improved behavioural performance in the open field test, forced swim test, and sucrose preference test, indicating a reversal of depression-like symptoms. Biochemical analyses showed that harmaline, consistent with its MAO-inhibitory activity, reduced serum corticosterone levels and increased brain concentrations of monoamines, namely, serotonin, norepinephrine, and dopamine, involved in mood regulation. Additionally, harmaline attenuated oxidative stress by lowering malondialdehyde (MDA) levels and enhancing antioxidant defences such as catalase and glutathione. It also reduced pro-inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-6, suggesting an anti-neuroinflammatory effect. These outcomes were comparable to those seen with imipramine. Overall, the findings support harmaline’s potential as an agent for mitigating stress-induced depressive disorders through the modulation of monoamines, oxidative stress, and neuroinflammation.
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
Cites 2
- Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids Pharmacognosy Reviews/Bioinformatics Trends/Pharmacognosy review 2013
- beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO). Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association March 1, 2010