Project 467226

Depression is a debilitating illness affecting 20% of the population that is characterized by depressed mood and disrupted cognition. Compared to males, females are twice as likely to develop depression and experience more severe cognitive symptoms. One such cognitive symptom is negative cognitive bias, the interpretation of neutral situations as negative.Depression is associated with increased inflammation in the brain. We have found that following chronic stress, both male and female rats display depressive-like behaviours; however, only in females was an increase in inflammation associated with negative cognitive bias. This suggests that negative cognitive bias develops via an inflammatory mechanism in females but not males.Negative cognitive bias can be quantified using a task developed in the Galea lab. Rats are trained to associate one context with an electric shock and another with no shock. Rats are then placed in a neutral context and their fear response is recorded. Increased fear behaviour indicates negative cognitive bias. To determine the role of inflammation in the development of chronic stress-induced negative cognitive bias, we plan to block different components of inflammation throughout the stress process. The fear responses of animals that had inflammation blocked during stress will be compared to those of untreated animals.The proposed research will examine whether sex differences in inflammation in the brain regulate chronic stress-induced negative cognitive bias by preventing inflammation before the cognitive bias task. We predict that inflammation in the brain will regulate stress-induced negative cognitive bias in females but not in males.