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Lack of persistent effects of ketamine in rodent models of depression

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Abstract

Rationale

We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity.

Materials and methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

The technical help of Dr. A Wesolowska and Mrs. L Socha for carrying out experiment 3 is greatly appreciated. This work was funded by the Statutory Activity of Institute of Pharmacology, Polish Academy of Sciences and in part (experiments 1 and 2) by Merz Pharmaceuticals GmbH, Frankfurt am Main.

Disclosure/Conflict of interest

The authors declare that this work was funded by the Statutory Activity of Institute of Pharmacology, Polish Academy of Sciences and in part (experiments 1 and 2) by Merz Pharmaceuticals GmbH, Frankfurt am Main. Merz Pharmaceuticals, however, is not associated with any product used in this study.

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Authors and Affiliations

  1. Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland

    Piotr Popik & Tomasz Kos

  2. Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland

    Magdalena Sowa-Kućma & Gabriel Nowak

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  1. Piotr Popik
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  2. Tomasz Kos
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  3. Magdalena Sowa-Kućma
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  4. Gabriel Nowak
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Correspondence to Piotr Popik.

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Popik, P., Kos, T., Sowa-Kućma, M. et al. Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology 198, 421–430 (2008). https://doi.org/10.1007/s00213-008-1158-z

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  • DOI: https://doi.org/10.1007/s00213-008-1158-z

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