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 via PubMed
Summary
AI-generated from the abstractProlonged treatment with ketamine did not alleviate depressive-like behavior in female mice exposed to chronic unpredictable mild stress, but it did improve anxiety-like behaviors, short-term memory, and social interaction deficits. Ketamine also increased plasma oxytocin levels and oxytocin receptor expression while reducing nitro-oxidative stress markers in intestinal and hippocampal tissues. These results suggest that although short-term ketamine has antidepressant effects, its extended use does not adequately resolve depressive-like behavior in mice.
Study at a glance
| 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 |
| Keywords | Depression-associated behaviours Gut-brain axis Oxidative/nitrergic stress Oxytocin receptors |
| Citations | 4 |
| Key finding | 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.