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Behavioral Pharmacology of Ketamine: An Overview of Preclinical Studies

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Ketamine

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Abstract

The behavioral pharmacological effects of ketamine in animals have been reviewed. Ketamine does not cause remarkable behavioral changes at doses effective for the treatment of depressive behavior in animal models. However, a transient increase in spontaneous motor activity has been reported sometimes. Ketamine is effective for the recovery of behavior caused by chronic mild stress, social defeat stress, and so on. Several mechanisms underlying this effect have been proposed, but a conclusive answer has still not been presented. (R)-Ketamine is more potent and has longer-lasting antidepressant effects than the (S)-isomer. Ketamine produces diverse behavioral changes other than antidepressant effects, such as blunting fear, cognitive impairments, and social withdrawal. Behavioral changes related to schizophrenia-like symptoms such as impairment of prepulse inhibition of the acoustic startle response and impairment of latent inhibition have been reported. However, relatively high doses seem to be necessary to yield these effects. Several lines of preclinical evidence have also shown the reinforcing and rewarding properties of ketamine, which are relevant to the abuse liability. To overcome these side effects and to optimize its clinical efficacy as a rapid-onset antidepressant for treatment-resistant patients, detailed preclinical studies targeting proper dosing regimen for clinical applications will be important.

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Abbreviations

im:

Intramuscular

ip:

Intraperitoneal

iv:

Intravenous

sc:

Subcutaneous

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Acknowledgment

The author would like to thank Ms. Kikuyo Nakaoka, Department of Pharmacology, Kumamoto Laboratory, LSI Medience Corp., for conducting the functional observational battery experiment.

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Authors and Affiliations

  1. Department of Pharmacology, LSI Medience Corp, Tokyo, Japan

    Naoyuki Hironaka

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  1. Naoyuki Hironaka
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Editors and Affiliations

  1. Division of Clinical Neuroscience, Chiba University, Chiba, Japan

    Kenji Hashimoto

  2. Tokyo Metropolitan Institute of Medical, Tokyo, Japan

    Soichiro Ide

  3. Tokyo Metropolitan Institute of Medical, Tokyo, Japan

    Kazutaka Ikeda

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Hironaka, N. (2020). Behavioral Pharmacology of Ketamine: An Overview of Preclinical Studies. In: Hashimoto, K., Ide, S., Ikeda, K. (eds) Ketamine. Springer, Singapore. https://doi.org/10.1007/978-981-15-2902-3_6

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