RT Journal Article SR Electronic T1 Validation of Chronic Restraint Stress Model in Young Adult Rats for the Study of Depression Using Longitudinal Multimodal MR Imaging JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0113-20.2020 DO 10.1523/ENEURO.0113-20.2020 VO 7 IS 4 A1 Bhedita J. Seewoo A1 Lauren A. Hennessy A1 Kirk W. Feindel A1 Sarah J. Etherington A1 Paul E. Croarkin A1 Jennifer Rodger YR 2020 UL http://www.eneuro.org/content/7/4/ENEURO.0113-20.2020.abstract AB Prior research suggests that the neurobiological underpinnings of depression include aberrant brain functional connectivity, neurometabolite levels, and hippocampal volume. Chronic restraint stress (CRS) depression model in rats has been shown to elicit behavioral, gene expression, protein, functional connectivity, and hippocampal volume changes similar to those in human depression. However, no study to date has examined the association between behavioral changes and brain changes within the same animals. This study specifically addressed the correlation between the outcomes of behavioral tests and multiple 9.4 T magnetic resonance imaging (MRI) modalities in the CRS model using data collected longitudinally in the same animals. CRS involved placing young adult male Sprague Dawley rats in individual transparent tubes for 2.5 h daily over 13 d. Elevated plus maze (EPM) and forced swim tests (FSTs) confirmed the presence of anxiety-like and depression-like behaviors, respectively, postrestraint. Resting-state functional MRI (rs-fMRI) data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. Proton magnetic resonance spectroscopy revealed decreased sensorimotor cortical glutamate (Glu), glutamine (Gln), and combined Glu-Gln (Glx) levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume. Importantly, these changes parallel those found in human depression, suggesting that the CRS rodent model has utility for translational studies and novel intervention development for depression.