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 Peer reviewed DOI: 10.1016/j.psyneuen.2023.106370 via PubMed
Summary
Prolonged use of ketamine did not alleviate depressive-like behavior in mice exposed to chronic unpredictable mild stress, but it did improve anxiety-like behaviors, short-term memory, and social interactions. Additionally, ketamine treatment increased plasma oxytocin levels and expression of oxytocin receptors while reducing oxidative stress markers in the gut and brain tissues. These findings suggest that while ketamine has some benefits, its long-term effectiveness for depression is limited.
Study at a glance
| Population | female BALB/c mice |
|---|---|
| Key finding | Prolonged treatment with ketamine did not rescue depressive-like behavior in mice but improved associated anxiety-like behaviors, memory, and social interaction. |
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.