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An anxiety-like phenotype in mice selectively bred for aggression
Derrick L Nehrenberg1, Ramona M Rodriguiz, Michel Cyr
1Department of Psychology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Behavioural Brain Research
|May 12, 2009
Summary
Selective breeding created mice with high aggression and anxiety. These NC900 mice show reduced GABA(A) receptor alpha(2) subunit, suggesting a link between this protein and comorbid anxiety-aggression disorders.
Area of Science:
- Neuroscience
- Behavioral Genetics
Background:
- Selective breeding can isolate behavioral traits.
- Aggression and anxiety are often comorbid in psychiatric disorders.
Purpose of the Study:
- To investigate the neurobiological underpinnings of aggression and anxiety using selectively bred mice.
- To determine if anxiety-like behaviors are present in a high-aggression mouse line.
Main Methods:
- Bi-directional selective breeding to create distinct mouse lines (NC900 and NC100).
- Behavioral testing including open field, light-dark exploration, and zero maze.
- Pharmacological challenge with diazepam.
- Assessment of GABA(A) receptor binding and subunit protein levels (alpha(1), alpha(2), gamma(2)) in brain regions.
Main Results:
- NC900 mice exhibited high reactivity, aggression, and anxiety-like behaviors.
- NC900 mice showed reduced sensitivity to diazepam's anxiolytic effects but reduced reactivity and aggression.
- Reduced diazepam-sensitive GABA(A) receptor binding, specifically lower alpha(2) subunit protein levels, was observed in NC900 frontal cortex and amygdala.
Conclusions:
- Reduced GABA(A) receptor alpha(2) subunit protein in specific brain regions may contribute to the anxiety and aggression phenotype in NC900 mice.
- This mouse model offers insights into the neurobiology of comorbid anxiety and aggression relevant to psychiatric conditions.
