Behavioural habituation to novelty and brain area specific immediate early gene expression in female mice of two inbred strains

In mice, emotional adaptation might be assessed by changes in behavioural responses towards novelty over time (i.e. habituation), with non-adaptive anxiety being expressed by a lack of habituation. Recently we found that male 129P3/J mice showed such a profound lack of habituation in comparison to male BALB/c mice. From these results we concluded that male 129P3/J mice might model non-adaptive, i.e. pathological anxiety. As a first step in the process of assessing the generalizability of our results, we investigated whether these results were robust across gender. Therefore we replicated our previous study in female individuals. Results from the present study reveal behavioural habituation towards novelty, i.e. an adaptive phenotype in female BALB/c mice. In contrast, females of the 129P3/J strain were characterised by a lack of habituation, similar as their male counterparts. Compared to female BALB/c, female 129P3/J mice showed lower neural activity in brain areas known to regulate the integration of emotional and cognitive processes. Extending the results found in males, female 129P3/J mice revealed increased post-testing plasma corticosterone levels and higher neural activity in brain areas related to emotional processing than females of the BALB/c strain. Taken together our results demonstrate that both genders of the 129P3/J mouse strain are characterised by a non-adaptive anxiety phenotype, strengthening the hypothesis that the 129P3/J strain may be a promising (neuro)-behavioural model for pathological anxiety.

Research highlights
• Initially highly anxious female BALB/c mice reveal rapid habituation, i.e. adaptive anxiety.
• Initially low anxious female 129P3 reveal a lack of habituation, i.e. non-adaptive anxiety.
• Non-adaptive anxiety is paralleled by lower c-Fos activity in prelimbic cortex in 129P3 mice.
• Differences in integrating cognitive-emotional processes may account for the reported strain characteristics.