Single administration of agmatine reverses the depressive-like behavior induced by corticosterone in mice: Comparison with ketamine and fluoxetine.
Vivian B Neis, Luis B Bettio, Morgana Moretti, Priscila B Rosa, Gislaine Olescowicz, Daiane B Fraga, Filipe M Gonçalves, Andiara E Freitas, Isabella A Heinrich, Mark W Lopes, Rodrigo B Leal, Ana Lúcia S Rodrigues
Pharmacology, Biochemistry, and Behavior October 2018 DOI: 10.1016/j.pbb.2018.08.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Female mice subjected to chronic corticosterone administration |
| Interventions | Agmatine Fluoxetine Ketamine |
| Dose | Agmatine 0.1 mg/kg, p.o.; fluoxetine 10 mg/kg, p.o.; ketamine 1 mg/kg, i.p.; corticosterone 20 mg/kg, p.o. |
| Duration | Corticosterone for 21 days; single dose of test drugs on the last day |
| Measures | Tail suspension test (TST) |
| Topics | Esketamine Ketamine |
| Keywords | Agmatine Antidepressant Corticosterone Synaptic proteins |
| Key points | A single dose of agmatine, like ketamine, reversed corticosterone-induced depressive-like behavior in the tail suspension test, whereas fluoxetine did not. Synaptic protein levels did not appear to account for these behavioral effects, though the authors argue the results support a fast-acting antidepressant profile for agmatine. |
Abstract
Agmatine is a neuromodulator that has been proposed as a therapeutic strategy for the treatment of major depressive disorder (MDD). A previous study reported that agmatine caused a fast-acting effect in mice subjected to chronic mild stress without causing changes in the levels of synaptic proteins in the prefrontal cortex. We examined whether a single administration of agmatine is able to counteract the depressive-like behavior induced by chronic administration of corticosterone, a pharmacological model of stress, paralleled with the modulation of synaptic protein levels in the prefrontal cortex and hippocampus. Female mice received corticosterone (20 mg/kg, p.o.) for 21 days and, in the last day of treatment, were administered with a single dose of agmatine (0.1 mg/kg, p.o.), fluoxetine (10 mg/kg, p.o.; control for a conventional antidepressant) or ketamine (1 mg/kg, i.p.; control for a fast-acting antidepressant). Agmatine, similar to ketamine, reversed the depressive-like behavior induced by corticosterone in the tail suspension test (TST), an effect that was not observed in mice treated with fluoxetine. The immunocontent of GluA1 was increased by all the treatments in the hippocampus of control mice, whereas PSD95 was not significantly altered by treatments in any brain structure. Although the levels of synaptic proteins do not seem to account for the behavioral findings reported here, the present study provides clear evidence for the fast-acting antidepressant profile of agmatine in the TST, similar to ketamine.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review Frontiers in Psychiatry June 26, 2023
- Ketamine, but not guanosine, as a prophylactic agent against corticosterone-induced depressive-like behavior: Possible role of long-lasting pro-synaptogenic signaling pathway Experimental Neurology September 3, 2020
- Subthreshold doses of guanosine plus ketamine elicit antidepressant-like effect in a mouse model of depression induced by corticosterone: Role of GR/NF-κB/IDO-1 signaling. Neurochemistry International July 8, 2020
- Guanosine potentiates the antidepressant-like effect of subthreshold doses of ketamine: Possible role of pro-synaptogenic signaling pathway. Journal of Affective Disorders June 1, 2020
Cites 6
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- mTOR activation is required for the antidepressant effects of mGluR2/3 blockade The International Journal of Neuropsychopharmacology November 24, 2011
- Astrocytes activation contributes to the antidepressant-like effect of ketamine but not scopolamine. Pharmacology, Biochemistry, and Behavior July 2018
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
and 1 more in the library