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Lack of persistent effects of ketamine in rodent models of depression.

Piotr Popik, Tomasz Kos, Magdalena Sowa-Kućma, Gabriel Nowak

Psychopharmacology June 2008 DOI: 10.1007/s00213-008-1158-z (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Rats and mice
Interventions Ketamine Desipramine Apomorphine
Dose 50-160 mg/kg (single dose); 1.25-50 mg/kg (single dose, FST); 50 or 160 mg/kg twice daily for 2 weeks; desipramine 10 mg/kg
Duration Single dose with testing at 1 week or 2 weeks; chronic treatment for 2 weeks (twice daily)
Measures Forced swim test (FST), Tail suspension test (TST), apomorphine-evoked locomotor activity, cortical beta-adrenoceptor density
Topics Depression Esketamine Ketamine
Key points Ketamine did not produce enduring antidepressant-like effects in rats or mice one week after a single dose, and chronic two-week treatment did not alter apomorphine-evoked locomotor hyperactivity or cortical beta-adrenoceptor density. The authors report some tolerance to ketamine's antidepressant-like effect in the forced swim test alongside sensitization to its locomotor-stimulating effects, concluding ketamine lacks antidepressant-like behavioral or neurochemical effects after chronic treatment.

Abstract

We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity. One week after a single administration of ketamine (50-160 mg/kg), otherwise experimentally naive rats and mice were tested either in the forced swim test (FST) or the tail suspension test (TST). Other mice were also tested twice in the FST: immediately and 2 weeks after a single dose (1.25-50 mg/kg) of ketamine. In the next series of experiments, rats treated for 2 weeks twice daily with ketamine (50 or 160 mg/kg) or desipramine (10 mg/kg) were challenged with apomorphine and scored for locomotor activity and assayed for the density of cortical beta-adrenoceptors. The latter test was also carried out in rats that had received a single dose of ketamine (50 mg/kg) 1 week before the assay. The antidepressant-like (FST) and locomotor effects of ketamine (50 mg/kg) and desipramine (10 mg/kg) were assessed after their chronic (2 weeks, twice daily) administration as well. We report the lack of enduring antidepressant-like effect of ketamine in both rats and mice. A 2-week treatment with ketamine neither changed apomorphine-evoked locomotor hyperactivity nor did it decrease the density of cortical beta-adrenoceptors. However, some tolerance to the antidepressant-like effect of ketamine was noted in the FST, but it was accompanied by sensitization to its locomotor stimulatory effects. These data indicate that ketamine neither produces enduring antidepressant-like effects in rodents nor does it display antidepressant-like behavioral or neurochemical effects after chronic treatment.

Comparable studies

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

Study Year Design Participants
Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats 2020 Preclinical study
A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... 2011 Animal experimental study
Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress 2017 Preclinical animal study
Comparison of R-ketamine and rapastinel antidepressant effects in the social defeat stress model of depression Susceptible mice in the social defeat stress model 2016 Animal experimental study
Ketamine and its metabolite, (2R,6R)-HNK, restore hippocampal LTP and long-term spatial memory in the Wistar-Kyoto rat model of depression Wistar-Kyoto (WKY) rats and Wistar control rats 2020 Preclinical study

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