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

Daniel A. Vazquez-Matias, Erik F.J. de Vries, Cyprien G.J. Guerrin, Kavya Prasad, Janine Doorduin
Psychiatry Research. 2026-04-01; 358: 116951
DOI: 10.1016/j.psychres.2026.116951

Vazquez-Matias DA(1), de Vries EFJ(2), Guerrin CGJ(1), Prasad K(1), Doorduin J(1).

Author information:
(1)Department of Nuclear Medicine and Molecular Imaging, University Medical
Center Groningen, University of Groningen, Groningen, the Netherlands.
(2)Department of Nuclear Medicine and Molecular Imaging, University Medical
Center Groningen, University of Groningen, Groningen, the Netherlands.
Electronic address: .

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
[18F]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.

DOI: 10.1016/j.psychres.2026.116951
PMID: 41576488

Conflict of interest statement: Declaration of competing interest E.F.J. de
Vries declares financial support for contracted research not related to this
study, paid to the institution in the past 5 years, from Hoffmann-La Roche, Eli
Lilly, Bristol Myers Squibb, Ionis Pharmaceutical, Rodin Therapeutics, Lysosomal
Therapeutics, Novartis, Janssen-Cilag BV, GE Healthcare and GlaxoSmithKline. The
other authors declare no conflict of interest.