Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes.
Melanie Clarke, Sara Razmjou, Natalie Prowse, Zach Dwyer, Darcy Litteljohn, Rowan Pentz, Hymie Anisman, Shawn P. Hayley
Neuropharmacology January 2017 DOI: 10.1016/j.neuropharm.2016.04.021 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Rodents (rats or mice) exposed to acute restraint, lipopolysaccharide, or chronic unpredictable psychogenic stressors |
| Intervention | Ketamine |
| Measures | forced swim test (FST), sucrose preference test |
| Topics | Depression Ketamine Neuroplasticity Esketamine |
| Keywords | Cytokine Lps Stressor |
| Key findings | Acute ketamine produced antidepressant-like effects in the forced swim test that lasted 8 days after repeated treatment, while repeated ketamine increased adult hippocampal neurogenesis and dose-dependently reversed LPS-induced elevations of IL-1β and TNF-α. Ketamine had little effect on stressor-induced corticosterone, monoamine, or sucrose preference changes, suggesting its antidepressant action may involve neuroplasticity and inflammatory processes rather than typical neurochemical or hormonal stress responses. |
Abstract
Considerable recent attention has focused on the rapid antidepressant effects observed in treatment resistant patients produced by the NMDA receptor antagonist, ketamine. Surprisingly, the effects of ketamine in the context of stressor exposure, as well as the consequences of its chronic use are unclear. Thus, we assessed the impact of acute and repeated ketamine treatment together with acute [restraint or lipopolysaccharide (LPS)] or chronic (unpredictable different psychogenic challenges) stressor exposure. Importantly, acute ketamine treatment did provoke an antidepressant-like effect in a forced swim test (FST) and this effect lasted for 8 days following repeated exposure to the drug. Although acute restraint and LPS individually provoked the expected elevation of plasma corticosterone and brain-region specific monoamine variations, ketamine had no influence on corticosterone and had, at best, sparse effects on the monoamine changes. Similarly, ketamine did not appreciably influence the stressor induced neurochemical and sucrose preference alterations, it did however, dose-dependently reverse the LPS induced elevation of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Likewise, repeated ketamine administration increased adult hippocampal neurogenesis. These data indicate that repeated ketamine administration had greater behavioral consequences than acute treatment and that the drug might be imparting antidepressant effects through its effects on neuroplasticity and inflammatory processes rather than the typical neurochemical/hormonal factors affected by stressors. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
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- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
- Rodent ketamine depression-related research: Finding patterns in a literature of variability Behavioural Brain Research August 13, 2019
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Cites 17
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