Behavioral and [F-18] fluorodeoxyglucose micro positron emission tomography imaging study in a rat chronic mild stress model of depression

We investigated changes in behavior and brain glucose metabolism in a rat chronic mild stress (CMS) model of depression. The CMS model has been used to mimic depression in humans by using various chronic mild stressors in a 4 weeks period. In the present study, we have developed a combination of tests examining behavior (open field test) and hedonic measure (sucrose preference test) after exposure to CMS, and compared this to control non-stressed rats. We found that CMS induced behavioral changes, including decreased central and rearing activity, increased grooming and defecation, reduced body weight, and reduced relative sucrose intake. Moreover, our study suggests that CMS administered for 4 weeks activated left auditory cortex, while left piriform cortex, left inferior colliculus, septal nuclei and periaqueductal gray were deactivated. These changes in region of interest are left-right asymmetrical and lateralized in the left hemisphere. And activity deficits of depression are related with changes of brain activity in all brain regions showing significant changes by CMS in glucose metabolism. There are significant correlations for relative sucrose intake in left piriform cortex, left inferior colliculus and left auditory cortex, and for anxiety-related behavioral measures in septal nuclei and periaqueductal gray. There are lack of significant effects in the mean glucose metabolism of both hemispheres in hippocampus and amygdala induced by CMS possibly because of various reasons. Changes in glucose metabolism support the view that these significant brain regions are involved in chronic stress and depressive mood regulation. The results of this study might contribute to the awareness of changes in behavior and brain activity of depression induced by CMS.