Neuroinflammation does not exacerbate post-traumatic stress-disorder (PTSD)-like brain measures or behaviour after a traumatic event in male rats

Post-traumatic stress disorder (PTSD) is strongly linked to neuroinflammation, with immune activation in brain regions such as the amygdala and hippocampus potentially contributing to its long-term persistence. Yet, whether neuroinflammation experienced at the time of trauma can cause, or increase the likelihood of PTSD-like symptoms and central nervous system changes developing is currently untested. If concomitant neuroinflammation exacerbates PTSD risk, treating neuroinflammation immediately after trauma could be a strategy to prevent PTSD development. This study investigated whether an immune challenge, induced by lipopolysaccharide (LPS), could exacerbate PTSD-like behaviours and brain changes following trauma induced by footshock in male rats. As expected, LPS induced transient weight loss, increased the expression of inflammation-related genes in the amygdala and hippocampus and lead to inflammatory-associated morphological changes in microglia. Although footshock led to persistent fear memory, indicated by increased freezing in the situational reminder test, LPS did not enhance the fear memory response induced by footshock. In the elevated plus maze, footshock reduced exploratory behaviour, indicating heightened anxiety, but this was also not exacerbated by LPS. Likewise, the effects of footshock on markers of neuronal health in the amygdala and hippocampus were not changed by LPS. Our data therefore suggest that a prior immune challenge with LPS does not exacerbate PTSD-like behaviours or fear memory in rats, indicating the brain is resilient against inflammation heightening trauma responses.