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Related Experiment Video

Updated: Jan 4, 2026

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The 5-hydroxytryptamine 2A receptor agonists DOI and 25CN-NBOH decrease marble burying and reverse 8-OH-DPAT-induced

Anna U Odland1, Lea Jessen1, Jesper L Kristensen1

  • 1Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, 2100, Denmark.

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|November 7, 2019
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Summary

Psychedelic 5-Hydroxytryptamine 2A receptor (5-HT2AR) agonists reduce repetitive behaviors in mice, suggesting a therapeutic potential for treating conditions characterized by cognitive inflexibility.

Keywords:
5-HT2A receptor5-HydroxytryptamineCompulsivityMarble buryingPsychedelicsSpontaneous alternation behavior

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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Behavioral Science

Background:

  • Psychedelics targeting the 5-Hydroxytryptamine 2A receptor (5-HT2AR) show promise for psychiatric disorders.
  • Inhibition of rigid behaviors is a proposed mechanism for their therapeutic effects.
  • Understanding the role of 5-HT2AR in modulating repetitive behaviors is crucial.

Purpose of the Study:

  • To investigate the effects of 5-HT2AR agonists on compulsive-like behaviors in mice.
  • To examine if 5-HT2AR agonism can reduce repetitive digging and improve exploratory behavior.

Main Methods:

  • Adult male C57BL/6JOlaHsd mice were treated with two 5-HT2AR agonists: DOI and 25CN-NBOH.
  • Behaviors were assessed using the marble burying test (digging) and the Y-maze test (spontaneous alternation).
  • Effects on locomotor activity were also monitored to rule out non-specific inhibition.

Main Results:

  • Both DOI and 25CN-NBOH dose-dependently reduced digging behavior in the marble burying test, indicating anti-compulsivity.
  • These anti-compulsivity effects were not due to general locomotor suppression.
  • The 5-HT2AR agonists partially reversed the reduction in spontaneous alternation behavior caused by 8-OH-DPAT in the Y-maze.

Conclusions:

  • Agonism of 5-HT2AR effectively reduces repetitive behaviors, supporting its role in treating behavioral inflexibility.
  • This finding supports the development of 5-HT2AR-targeting therapies for psychiatric disorders characterized by rigidity.
  • The 5-HT2AR appears to promote exploratory behavior, though severe deficits may not be fully reversible.