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Review ArticleReview Article

Animal Behavior in Psychedelic Research

Anna U. Odland, Jesper L. Kristensen and Jesper T. Andreasen
Lynette Daws, ASSOCIATE EDITOR
Pharmacological Reviews October 2022, 74 (4) 1176-1205; DOI: https://doi.org/10.1124/pharmrev.122.000590
Anna U. Odland
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark
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Jesper L. Kristensen
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark
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Jesper T. Andreasen
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark
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Lynette Daws
Roles: ASSOCIATE EDITOR
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Abstract

Psychedelic-assisted psychotherapy holds great promise in the treatment of mental health disorders. Research into 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist psychedelic compounds has increased dramatically over the past two decades. In humans, these compounds produce drastic effects on consciousness, and their therapeutic potential relates to changes in the processing of emotional, social, and self-referential information. The use of animal behavior to study psychedelics is under debate, and this review provides a critical perspective on the translational value of animal behavior studies in psychedelic research. Acute activation of 5-HT2ARs produces head twitches and unique discriminative cues, disrupts sensorimotor gating, and stimulates motor activity while inhibiting exploration in rodents. The acute treatment with psychedelics shows discrepant results in conventional rodent tests of depression-like behaviors but generally induces anxiolytic-like effects and inhibits repetitive behavior in rodents. Psychedelics impair waiting impulsivity but show discrepant effects in other tests of cognitive function. Tests of social interaction also show conflicting results. Effects on measures of time perception depend on the experimental schedule. Lasting or delayed effects of psychedelics in rodent tests related to different behavioral domains appear to be rather sensitive to changes in experimental protocols. Studying the effects of psychedelics on animal behaviors of relevance to effects on psychiatric symptoms in humans, assessing lasting effects, publishing negative findings, and relating behaviors in rodents and humans to other more translatable readouts, such as neuroplastic changes, will improve the translational value of animal behavioral studies in psychedelic research.

SIGNIFICANCE STATEMENT Psychedelics like LSD and psilocybin have received immense interest as potential new treatments of psychiatric disorders. Psychedelics change high-order consciousness in humans, and there is debate about the use of animal behavior studies to investigate these compounds. This review provides an overview of the behavioral effects of 5-HT2AR agonist psychedelics in laboratory animals and discusses the translatability of the effects in animals to effects in humans. Possible ways to improve the utility of animal behavior in psychedelic research are discussed.

Footnotes

    • Received February 15, 2022.
    • Accepted June 30, 2022.
  • This work was supported by Lundbeckfonden for the PhD project of Odland [Grant R263-2017-3000]. Kristensen is cofounder and CSO of Lophora, which is pursuing novel psychedelics as treatment of various disorders.

  • dx.doi.org/10.1124/pharmrev.122.000590.

  • Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 74 (4)
Pharmacological Reviews
Vol. 74, Issue 4
1 Oct 2022
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Review ArticleReview Article

Animal Behavior in Psychedelic Research

Anna U. Odland, Jesper L. Kristensen and Jesper T. Andreasen
Pharmacological Reviews October 1, 2022, 74 (4) 1176-1205; DOI: https://doi.org/10.1124/pharmrev.122.000590

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Review ArticleReview Article

Animal Behavior in Psychedelic Research

Anna U. Odland, Jesper L. Kristensen and Jesper T. Andreasen
Pharmacological Reviews October 1, 2022, 74 (4) 1176-1205; DOI: https://doi.org/10.1124/pharmrev.122.000590
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  • Article
    • Visual Overview
    • Abstract
    • I. Background
    • II. Behaviors That Predict 5-HT2AR Activation
    • III. Animal Behaviors with Possible Phenomenological Relatedness to Psychedelic Effects in Humans
    • IV. Perspectives on Animal Behavior in Psychedelic Research
    • V. Strengths and Limitations of This Review
    • VI. Conclusion
    • Acknowledgments
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