Sex Differences in Anhedonic and Anxiety-like Behavioral Responses to Predator Odor-Exposure in Toll-like Receptor 4 (TLR4) Gene Knockout and Wild Type Rats

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A growing body of evidence demonstrates the role of inflammation in stress-related disorders. Toll-like receptor 4 (TLR4) is one receptor type involved in innate immune responses to stress and may play a role in some aspects of these disorders. In patients with major depressive disorder, levels of TLR4 expression correlate with severity of certain symptoms, specifically anxiety and weight loss, and decrease with treatment by antidepressant medication or cognitive behavioral therapy. However, at the time of this study, no published research has explored the role of TLR4 in either depressive or anxiogenic symptomology in response to a traumatic stressor. Unpublished work by our group utilizing TLR4 gene knockout rats suggests that TLR4 activation alters anxiety-like behavior in a rodent model of post-traumatic stress disorder. Continuing from these findings in the predator odor-exposure stress model, we have added non-exposed control groups of both genotypes in order to further examine the significance of these findings. Both male and female animals exhibited increased anxiety-like and aversive behavior after controlled exposure to predator odor, with specific behavioral effects differing by sex and genotype. This was evident over all behaviors measured.