Age increases anxiety and reactivity of the fear/anxiety circuit in Lewis rats

A growing body of data indicates that changes in emotional behavior occur with age. Young Lewis rats are known to display hypofunction of the HPA axis. With age the reactivity of this axis is thought to increase with a concomitant rise in anxiety. In the current study, we investigate how and if the pattern of neuronal activation (measured as c-Fos protein expression) in Lewis rat brains changes with age and in response to novel environments differing in aversiveness. We found that distinct parts of the fear/anxiety circuit (i.e., the amygdalar complex, hippocampus and hypothalamus) undergo diverse age-related changes in response to behavioral challenges. While in the hypothalamus an increase in responsivity to mild stressors was observed with age, no such effect was present in the hippocampus. The amygdalar complex (especially the medial and cortical nuclei) on the other hand exhibited an age-dependent decrease in neuronal activation to mild stressors. This was accompanied by a marked increase in anxiety not correlated with a decline in locomotor activity.

► Ageing influences both the pattern of neuronal activation and the anxiety-related behavior of Lewis rats.
► The distinct parts of the fear/anxiety circuit (the amygdalar complex, hippocampus and hypothalamus) undergo diverse age-related changes in reactivity to behavioral challenges.
► The initial hypofunction of the HPA axis of Lewis rats is abolished by age.
► The amygdalar complex experiences an age-dependent decrease in reactivity to mild stressors.
► The Principal Component Analysis reveals that the age-related increase in anxiety is independent of the decrease in locomotor activity.