Identifying emotional adaptation: behavioural habituation to novelty and immediate early gene expression in two inbred mouse strains

Abstract

Normal anxiety is an adaptive emotional response. However, when anxiety appears to lack adaptive value, it might be defined as pathological. Adaptation in animals can be assessed for example by changes in behavioural responses over time, i.e. habituation. We hypothesize that non-adaptive anxiety might be reflected by impaired habituation. To test our hypothesis, we repeatedly exposed male mice from two inbred strains to a novel environment, the modified hole board. BALB/cJ mice were found to be initially highly anxious, but subsequently habituated to the test environment. In contrast, 129P3/J mice initially showed less anxiety-related behaviour compared with the BALB/cJ mice but no habituation in anxiety-related behaviour was observed. Notably, anxiety-related behaviour even increased during the experimental period. Complementary, 129P3/J mice did not show habituation in other parameters such as locomotor and exploratory activity, whereas significant changes appeared in these behaviours in BALB/c mice. Finally, the expression of the immediate early gene c-fos differed between the two strains in distinct brain areas, known to regulate the integration of emotional and cognitive processes. These results suggest that 129P3/J mice might be a promising (neuro)-behavioural animal model for non-adaptive, i.e. pathological anxiety.

A test to identify judgement bias in mice

“…4). 129P3 mice revealed rapidly decreasing latencies to approach all odour cups after a few training trials in both odour conditioning tasks, showing that 129P3 mice are able to learn the spatial location of a reward, a finding that confirms earlier results of our lab showing that these mice are relatively fast in learning the location of reward in the modified hole board test [30,47]. However, 129P3 mice did not seem to build any negative association with the odour predictive for the bitter-tasting almond piece readily as indicated by comparable response times to different odours in the test session.…”

“…From now on this apparatus will be called the odour cylinder. The odour cylinders are similar to those used in the modified hole board and suitable for mice (see for example [30]). Odours (0.05 ml) were spread on a filter paper ( 3.2 cm) that fitted underneath the cylinder.…”

“…Initially in our first experiment a one-trial learning procedure was applied (one NEG trial) in order to minimize the number of aversive trials, since we have previously found that mice from the 129P3/J strain have difficulties to habituate to a mildly aversive environment [30,30,47]. As we continued with BALB/c in experiment 2, some extra trials were added to insure that the animals learned the odour associations.…”

“…Recently anxiety-related behaviour in two inbred mouse strains, BALB/cJ (BALB/c) and 129P3/J (129P3) was evaluated in our lab and it appeared that BALB/c mice behave highly anxious when initially exposed to a test environment, but show a rapid habituation over time, while 129P3 mice are initially less anxious but do not habituate to the testing environment [30,31]. Previously, BALB/c mice have been suggested to represent a phenotype of trait anxiety because they show high state anxiety in multiple testing situations [30,[32][33][34].…”

“…Previously, BALB/c mice have been suggested to represent a phenotype of trait anxiety because they show high state anxiety in multiple testing situations [30,[32][33][34]. Thus to our first aim we performed the test in these previously characterised 129P3 and BALB/c mice (experiment 1) expecting a more negative judgement of the initially highly anxious BALB/c mice.…”