Modeling mania: Further validation for Black Swiss mice as model animals

The paucity of appropriate animal models for bipolar disorder hinders the research of the disorder and its treatments. Previous work suggests that Black Swiss (BS) mice may be a suitable model animal for behavioral domains of mania including reward-seeking, risk-taking, vigor, aggression and sensitivity to psychostimulants. These behaviors are high in BS mice compared with other strains and are responsive to the mood stabilizers lithium and valproate but not to the antidepressant imipramine. The current study evaluated the etiological validity of this model by assessing brain expression of two proteins implicated in affective disorders, β-catenin and BDNF, in BS mice versus C57bl/6, A/J and CBA/J mice. Additionally, pharmacological validity was further tested by assessing the effects of risperidone in a behavioral battery of tests. β-catenin and BDNF expression were evaluated in the frontal cortex and hippocampus of untreated BS, CBA/J, A/J and C57bl/6 mice by western blot. Subchronic 0.1 and 0.3mg/kg doses of risperidone were tested in a battery of behavioral tests for domains of mania. Expression of β-catenin was found to be lower in the hippocampus of BS mice compared with the other strains. Reduced β-catenin expression was not observed in the frontal cortex. BDNF expression levels were similar between strains in both the hippocampus and frontal cortex. In the behavioral tests, risperidone ameliorated amphetamine-induced hyperactivity without affecting other tests in the battery. These results offer additional pharmacological and possible etiological validity supporting the utilization of Black Swiss mice as a model for domains of mania.