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A new mouse model of ADHD for medication development.

Petra Majdak1,2, John R Ossyra3, Jessica M Ossyra4

  • 1The Neuroscience Program, University of Illinois, IL, USA.

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|December 21, 2016
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Researchers developed a new mouse model for Attention Deficit Hyperactivity Disorder (ADHD). This High-Active line exhibits key ADHD symptoms and can aid in developing new ADHD treatments.

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Area of Science:

  • Neuroscience
  • Behavioral Science
  • Genetics

Background:

  • Attention Deficit Hyperactivity Disorder (ADHD) presents a significant societal challenge with rising incidence.
  • Limited progress in ADHD treatment is partly due to a lack of suitable animal models.
  • Developing novel animal models is crucial for advancing ADHD research and therapeutic development.

Purpose of the Study:

  • To generate a novel mouse model for Attention Deficit Hyperactivity Disorder (ADHD) to facilitate medication development.
  • To investigate if core ADHD features, beyond hyperactivity, emerge as correlated responses in a selectively bred population.
  • To establish a resource for studying ADHD etiology and screening potential treatments.

Main Methods:

  • Utilized within-family selection over 16 generations from a heterogeneous population to create a High-Active mouse line.
  • Maintained an unselected line as a Control group for comparative analysis.
  • Assessed motor impulsivity using two versions of the Go/No-go test.
  • Examined brain activity via c-Fos immunohistochemical staining to analyze prefrontal cortex and cerebellar vermal activation.

Main Results:

  • The High-Active line exhibited significant motor impulsivity in Go/No-go tests.
  • Low-dose amphetamine administration ameliorated the observed motor impulsivity in the High-Active line.
  • Neuroimaging revealed hypoactivation in the prefrontal cortex and dysregulated activation in the cerebellar vermis of the High-Active line.
  • These findings indicate distinct neurobiological correlates associated with the behavioral phenotype.

Conclusions:

  • The developed High-Active mouse line serves as a valid preclinical model for the Hyperactive-Impulsive subtype of ADHD.
  • This model can be instrumental in future research to elucidate ADHD's underlying causes.
  • The model provides a platform for screening novel therapeutic compounds for ADHD treatment.