Evidence map›Paper›PMID 42452983›Full record

ArticleIranian biomedical journal2026

Antidepressant Effects of L-Arginine and Its Role in Brain Energy Metabolism

T Mantashashvili, L Nakaidze, M Shengelia, N Koshoridze

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Article in Iranian biomedical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

T MantashashviliDepartment of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia.
L NakaidzeDepartment of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia.
M ShengeliaDepartment of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia.
N KoshoridzeDepartment of Biology, Ivane Javakhishvili Tbilisi State University, 11th Building, University Street, 0186, Tbilisi, Georgia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Mitochondrial dysfunction and impaired cellular energy metabolism are increasingly recognized as key contributing factors in depression. This study evaluated the amino acid L-arginine as a potential agent for behavioral rescue and bioenergetic restoration using a corticosterone-induced rat model of depression. Methods: Male rats were randomly assigned to four groups (n = 10): control (DMSO intraperitoneally [i.p.] + water oral gavage), corticosterone-induced depression (20 mg/kg, i.p. for 14 days), L-arginine treatment (150 mg/kg, oral gavage for 14 days), and fluoxetine (10 mg/kg, oral gavage for 14 days). To ensure handling equivalence, all oral administrations were performed via gavage (1.0 mL/100 g). Behavioral rescue was assessed via open field, forced swim (FST), and tail suspension (TST) tests. Hippocampal energy metabolism and PI3K/Akt/mTOR pathway activation were analyzed. Results: L-arginine significantly improved the hippocampal bioenergetic profile, demonstrating efficacy comparable to the positive control fluoxetine. It led to a significant reduction in immobility time during FST and TST, alongside restoring glycolysis, the tricarboxylic acid cycle, and mitochondrial respiratory chain activities. Concurrently, L-arginine enhanced the activation state of the PI3K/Akt/mTOR signaling pathway (phosphorylated Akt/Akt and p-mTOR/mTOR ratios) and improved the functional state of the mitochondrial permeability transition pore. These metabolic and signaling improvements strongly correlated with the rescue of depressive-like behaviors. Concludion: Our findings demonstrate that L-arginine possesses potent antidepressant-like potential, mediated through bioenergetic restoration and signaling pathway modulation. By activating key metabolic processes in the hippocampus, L-arginine effectively restores impaired cellular energy homeostasis, suggesting its promise as a metabolic modulator for alleviating neurobiological disturbances associated with depressive conditions.

Indexed as

Antidepressive AgentsArginineBrainDepressionEnergy MetabolismAnimalsBehavior, AnimalCorticosteroneHippocampusMalePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRatsSignal TransductionSwimmingTOR Serine-Threonine KinasesAntidepressive AgentsArginineCorticosteronePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinases

Identifiers

PMID42452983
PMCPMC13539223

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.