High trait anxiety in mice is associated with impaired extinction in the contextual fear conditioning paradigm

Trait anxiety is a form of chronic state anxiety that can be part of the individual's personality and one of the individual factors that increase the risk of developing PTSD. To be able to distinguish between trait and state anxiety in animal models might be challenging, since the tests themselves are often anxiogenic. One possible approach is the use of the free exploratory paradigm (FEP), a model that consists of providing the animal the choice to explore both a familiar and a novel environment. High trait anxiety animals choose to explore more the familiar environment. Thus, the objective of this study was to evaluate if differences in trait anxiety could lead to impairments in acquisition and extinction of fear memory in a contextual fear conditioning protocol. First, Swiss mice were divided into high trait anxiety (HTA) or low trait anxiety (LTA) based on their exploration of the novel environment (%TNS) in the FEP. We observed that the %TNS was stable across three testing sessions. Also, we observed that freezing behavior was not different between HTA and LTA mice in a retrieval session 1 day after the conditioning, which indicates that acquisition was not impaired. However, HTA presented higher freezing time during extinction training and test. Also, HTA presented higher freezing in reinstatement test, but this might be related to the poor extinction learning. Moreover, diazepam (0.25 or 1.0 mg/kg, i.p.) did not prevent the differences in extinction training and test when administer 30 min before conditioning training or 30 min before extinction training, even though diazepam (1.0 mg/kg) had anxiolytic effect in the elevated plus-maze. These results demonstrate that HTA mice presented increase in freezing during extinction training and test, as well as during reinstatement. These results indicate that increased freezing time in HTA mice is not explained by high state anxiety in a specific phase of the fear conditioning, but more likely, the overall high trait anxiety throughout the entire experiment.