Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression
Nico Liebenberg, Sâmia R L Joca, Gregers Wegener
Acta Neuropsychiatrica April 1, 2015 DOI: 10.1017/neu.2014.39 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Flinders sensitive line (FSL) rats |
| Interventions | Ketamine L-arginine |
| Dose | 15 mg/kg ketamine, 500 mg/kg L-arginine |
| Topics | Depression Esketamine Ketamine |
| Key findings | L-arginine pre-treatment prevented the antidepressant-like effect of ketamine in the forced swim test and blocked ketamine-induced increases in cGMP levels in the frontal cortex and hippocampus. |
Abstract
ObjectiveWe investigated whether the nitric oxide (NO) precursor,l-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-d-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine.MethodsFlinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) withl-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluatedex vivoin the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration.Resultsl-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed byl-arginine.ConclusionBoth the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 11
- Psilocybin lacks antidepressant-like effect in the Flinders Sensitive Line rat Acta Neuropsychiatrica May 20, 2019
- S-Ketamine Rapidly Reverses Synaptic and Vascular Deficits of Hippocampus in Genetic Animal Model of Depression The International Journal of Neuropsychopharmacology November 2, 2016
- Metabolomic correlates of intravenous racemic ketamine in treatment-resistant major depressive disorder: the Bio-K/NNDC multicenter trial The World Journal of Biological Psychiatry September 6, 2026
- Single dose S-ketamine rescues transcriptional dysregulation of Mtor and Nrp2 in the prefrontal cortex of FSL rats 1hour but not 14 days post dosing. European Neuropsychopharmacology November 11, 2022
- Ketamine reversed short-term memory impairment and depressive-like behavior in animal model of Parkinson's disease. Brain Research Bulletin December 22, 2020
and 6 more in the library
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
- 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 Journal of Neuroscience April 15, 1997
- Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology January 2012
- Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry February 15, 2008
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