Characterisation of non-adaptive anxiety in two inbred mouse strains. Frontiers in Behavioral Neuroscience

Anxiety is an adaptive emotional response but when anxiety appears to lack adaptive value, it might be defined as pathological. As adaptation in animals can be assessed for example by changes in behavioural responses over time, i.e. habituation, pathological anxiety might be characterised as impaired habituation. To evaluate this hypothesis, we investigated habituation-profiles in two inbred mouse strains. Initially highly anxious male BALB/c mice showed rapid habituation towards a novel environment shown by a decrease in avoidance behaviour, which was paralleled by an increase in exploratory and locomotor activity, respectively. In contrast, 129P3/J mice lacked habituation under the same circumstances. Notably, under more aversive conditions, 129P3/J mice even seem to sensitise to the test conditions, indicated by increased avoidance-behaviour. This reaction was not paralleled by increased levels of the stress hormone corticosterone, suggesting that the sustained avoidance behaviour in129P3/J mice was a successful strategy for avoiding stress. Further, the expression of the immediate early gene, c-fos, a marker for neural activity, was lower in specific brain areas (e.g. prelimbic cortex and lateral septum) of 129P3/J compared to BALB/c mice. These results suggest that the integration of emotional and cognitive processes may be impaired in 129P3/J mice. To explore whether anxiety is primarily regulating the behavioural characteristic, both strains were treated with diazepam. In the open field test, acute anxiolytic treatment resulted in normalisation of within-trial habituation in 129P3/J, while the habituation profile in BALB/c animals remained unaffected. These results indicate that 129P3/J mice might be an interesting animal model for pathological anxiety. However, further investigation of the central nervous mechanisms underlying the non-adaptive behavioural profile of 129P3/J mice is necessary to validate this mouse strain as a model for pathological anxiety