Metabolic brain connectivity analysis of a depressive-like phenotype in rats: a graph theory PET study

This study aimed to investigate whether there are metabolic connectivity alterations in the brain of rats with a depressive-like phenotype, using positron emission tomography (PET) and graph theory methods. Male Wistar rats were exposed to 5 days of repeated social defeat (RSD) to induce a depressive-like phenotype, and brain connectivity was assessed with [ 18 F]FDG-PET. Sucrose preference tests were conducted to assess anhedonia-like behaviour, a symptom of depression. The results showed that anhedonia-like behaviour was present one day after RSD and recovered after seven days. The analysis of large-scale brain networks revealed a reduction in connectivity in the default mode network of RSD-exposed animals one day after RSD, suggesting a link between reduced connectivity and the presence of anhedonia-like behaviour. Seven days after RSD, an increase in connectivity was observed in the salience network, which coincided with the recovery of sucrose preference. Modular analysis revealed different configurations of brain regions at one and seven days after RSD, with asymmetrical segregation of left and right hemisphere structures. These findings suggest that changes in brain connectivity may play a role in the development and recovery of anhedonia-like behaviour in rats exposed to RSD and may have implications for understanding depressive phenotypes.