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Evidence for Distinct Forms of Compulsivity in the SAPAP3 Mutant-Mouse Model for Obsessive-Compulsive Disorder.

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  • 1Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands.

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Summary

Mice models of obsessive-compulsive disorder (OCD) were tested using the signal attenuation (SA) task. SAPAP3 knockout mice, exhibiting OCD-like behaviors, did not show enhanced compulsive responses, suggesting independent mechanisms for different compulsivity types.

Keywords:
SAPAP3 knock-out micecompulsivityfeedback processingobsessive-compulsive disordersignal attenuation

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Area of Science:

  • Neuroscience
  • Animal Models
  • Cognitive Psychology

Background:

  • Obsessive-compulsive disorder (OCD) mechanisms remain unclear, with theories suggesting cognitive dysfunction in feedback processing.
  • The signal attenuation (SA) task models feedback processing deficits by reducing reward association with post-action feedback.
  • While established in rats, the SA task's utility in mice, crucial for genetic OCD models, was unconfirmed.

Purpose of the Study:

  • To validate the SA task in mice for modeling cognitive deficits relevant to OCD.
  • To investigate if SAPAP3 knockout mice, known for OCD-like grooming, exhibit heightened compulsive behavior in the SA task.
  • To explore the relationship between feedback processing deficits and excessive grooming in SAPAP3 knockout mice.

Main Methods:

  • Implemented the SA task in C57BL/6 mice, attenuating audiovisual feedback associated with reward after operant responses.
  • Compared compulsive-like behavior in SAPAP3 knockout mice (SAPAP3-/-) with wild-type (WT) littermates within the SA task paradigm.
  • Assessed behavioral responses during both SA-induced feedback distortion and standard extinction phases of operant behavior.

Main Results:

  • Successfully adapted the SA task to mice, demonstrating that feedback attenuation induced compulsive-like responding comparable to rats.
  • SAPAP3 knockout mice did not show significantly different compulsive behaviors compared to WT littermates in the SA task.
  • No significant differences in compulsivity measures were observed between SAPAP3-/- and WT mice during SA or regular extinction phases.

Conclusions:

  • The SA task is a viable model for studying feedback processing deficits in mice relevant to OCD.
  • Compulsive-like instrumental behavior following feedback distortion is not potentiated in SAPAP3 knockout mice.
  • Excessive grooming in SAPAP3 knockout mice is likely independent of the general feedback processing deficits modeled by the SA task, suggesting distinct mechanisms for different OCD-related compulsions.