ABNORMALITIES OF THE LURCHER MOUSE, A MODEL OF CEREBELLAR MOTOR AND COGNITIVE AFFECTIVE SYNDROME, AND DIAZEPAM TREATMENT FOR STRESS REACTIVITY

Lurcher mice (Lc), a model of cerebellar cognitive affective syndrome (CCAS), exhibit stress-induced behavioral disinhibition due to selective olivocerebellar degeneration. The aim of the study was to investigate cognitive and behavioral abnormalities and the expression of stress-related genes, with and without diazepam (an anxiolytic compound) administration.
Lc and wild-type (WT) B6CBA mice aged 4-6 months were used. The mice were injected with diazepam (0.5mg/kg, 1.0mg/kg, or 2.0mg/kg) or saline 30 minutes prior to the behavioral paradigms: open field, elevated plus maze, pre-pulse inhibition, grip-strength measurement, and rotarod. Spatial behavior and memory were examined in the Morris water maze and linear track. To evaluate gene expression, cortex, hippocampus, and amygdala were collected from undisturbed and stressed mice (stress induced by a 5-minute forced swimming).
The effect of diazepam was observed in a scattered manner across groups, without any common trends across behavioral paradigms. Diazepam treatment didn’t reduce behavioral abnormalities in Lc. Lc mice performed worse in reaching the platform in the Morris water maze, especially when the goal was visible. They also showed reduced space exploration activity. Preliminary data showed that changes of gene expression in response to stress and diazepam treatment were predominantly in the hippocampus compared with other parts.
Spatial orientation and space exploration were impaired in Lc mice. Diazepam didn’t induce any major improvement in signs of the CCAS in Lc but influenced stress-related gene expression in the hippocampus.
The study was supported by GAUK No. 49724, SVV 262774, and Cooperatio (research area NEUR).