Prolonged ketamine therapy differentially rescues psychobehavioural deficits via modulation of nitro-oxidative stress and oxytocin receptors in the gut-brain-axis of chronically-stressed mice.

Edem Ekpenyong Edem; Oluwatomisn Adeyosola Oguntala; Daniel Akinwale Ikuelogbon; Kate Eberechukwu Nebo; Adedamola Adediran Fafure; Elizabeth Toyin Akinluyi; Godspower Tochukwu Isaac; Oladunni Eunice Kunlere

doi:10.1016/j.psyneuen.2023.106370

Prolonged ketamine therapy differentially rescues psychobehavioural deficits via modulation of nitro-oxidative stress and oxytocin receptors in the gut-brain-axis of chronically-stressed mice.

Edem Ekpenyong Edem, Oluwatomisn Adeyosola Oguntala, Daniel Akinwale Ikuelogbon, Kate Eberechukwu Nebo, Adedamola Adediran Fafure, Elizabeth Toyin Akinluyi, Godspower Tochukwu Isaac, Oladunni Eunice Kunlere

Psychoneuroendocrinology December 1, 2023 DOI: 10.1016/j.psyneuen.2023.106370 (opens in new tab)

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AI-extracted from the abstract

Characteristics	Randomized controlled trial Peer reviewed
Population	Female BALB/c mice
Intervention	Ketamine
Dose	four doses
Duration	14-day treatment after 21-day CUMS or simultaneous treatment during last two weeks of CUMS
Topics	Ketamine Esketamine
Keywords	Depression-associated behaviours Gut-brain axis Oxidative/nitrergic stress Oxytocin receptors
Citations	4
Key findings	Prolonged ketamine treatment did not rescue depressive-like behavior but improved anxiety, memory, and social deficits, and enhanced oxytocin signaling while reducing oxidative stress.

Abstract

Ketamine is an anaesthetic known to have short but rapid-acting anti-depressant effects; however, the neurobehavioural effects of its prolonged use and its role on the oxytocin system in the gut-brain axis are largely undetermined. Female BALB/c mice were either exposed to the chronic unpredictable mild stress (CUMS) paradigm for 21 days and then treated with ketamine in four doses for 14 days or exposed to CUMS and treated simultaneously in four doses of ketamine during the last two weeks of CUMS exposure. After each dose, the forced swim test was conducted to assess depressive-like behaviour. Before sacrifice, all the mice were subjected to behavioural tests to assess anxiety, memory, and social interaction. Prolonged treatment of depression with ketamine did not rescue depressive-like behaviour. It did, however, improve depression-associated anxiety-like behaviours, short-term memory and social interaction deficits when compared to the stressed untreated mice. Furthermore, ketamine treatment enhanced plasma oxytocin levels, expression of oxytocin receptors; as well as abrogated nitro-oxidative stress biomarkers in the intestinal and hippocampal tissues. Taken together, our findings indicate that while short-term use of ketamine has anti-depressant benefits, its prolonged therapeutic use does not seem to adequately resolve depressive-like behaviour in mice.

Comparable studies

Other preclinical and animal studies on ketamine, most cited first.

Study	Year	Design
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

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