Neuroinflammation in the prefrontal-amygdala-hippocampus network is associated with maladaptive avoidance behaviour.

ABSTRACT

Maladaptive avoidance behaviour is often observed in patients suffering from anxiety and trauma- and stressor-related disorders. The prefrontal-amygdala-hippocampus network is implicated in learning and memory consolidation. Neuroinflammation in this circuitry alters network dynamics, resulting in maladaptive avoidance behaviour. The two-way active avoidance test is a well-established translational model for assessing avoidance responses to stressful situations. While some animals learn the task and show adaptive avoidance (AA), others show strong fear responses to the test environment and maladaptive avoidance (MA). Here, we investigated if a distinct neuroinflammation pattern in the prefrontal-amygdala-hippocampus network underlies the behavioural difference observed in these animals. Wistar rats were tested 8 times and categorized as AA or MA based on behaviour. Brain recovery followed for the analysis of neuroinflammatory markers in this network. AA and MA presented distinct patterns of neuroinflammation, with MA showing increased astrocyte, EAAT-2, IL-1ß, IL-17 and TNF-ɑ in the amygdala. This neuroinflammatory pattern may underlie these animals' fear response and maladaptive avoidance. Further studies are warranted to determine the specific contributions of each inflammatory factor, as well as the possibility of treating maladaptive avoidance behaviour in patients with psychiatric disorders with anti-inflammatory drugs targeting the amygdala.