BRAIN-WIDE METABOLIC CHANGES ASSOCIATED WITH CHRONIC CORTICOSTERONE ADMINISTRATION IN RATS

Chronic stress-induced anxiety is a highly prevalent condition in the general population, with
detrimental effects on one’s body and the brain. However, 10-30%, of those affected, do not respond
to the currently available medications. It is therefore of crucial importance to elucidate the mechanism
of chronic stress-induced anxiety and possibly contribute to the development of novel treatment
options. This project investigates the progression and pathology of chronic stress at a whole-brain
level.
We examined the development of chronic stress-induced anxiety using a corticosterone (CORT)
animal model in Long Evans rats. To assess changes in brain metabolic demands associated with
chronic stress exposure, [18F]-FDG positron emission tomography (PET) was performed. PET scans
were acquired at baseline and after 21 days of CORT exposure (20 mg/kg; n = 8) or vehicle
administration (n=7).
Following CORT exposure, we observed hypometabolism in the cingulate cortex and orbitofrontal
cortex. In contrast, increased FDG uptake was detected in stress-related regions including the
amygdala, ventral hippocampus and hypothalamus after the 21-day CORT intervention (two-way
ANOVA, p<0.05). These metabolic alterations were not observed in the control group. Metabolic
covariance analysis further revealed a disruption of negative correlations between the medial
prefrontal cortex and hippocampus following CORT administration.
In conclusion, this project contributes to the characterization of metabolic covariance changes
underlying the progression of chronic stress-induced anxiety. These findings provide insight into
stress-related network pathology and may identify potential circuit-level mechanisms relevant for
future therapeutic approaches.