Validation of chronic restraint stress model in rats for the study of depression using longitudinal multimodal MR imaging

Abstract

Prior research suggests that the neurobiological underpinnings of depression include disruptions in functional connectivity, neurometabolite levels, and hippocampal volume. This study examined the validity of a chronic restraint stress (CRS) paradigm in male Sprague Dawley rats for the study of depression using longitudinal behavioural tests and multiple 9.4 T MRI modalities (resting-state functional MRI, proton magnetic resonance spectroscopy, and volumetric studies). In the CRS protocol, rats were placed in individual transparent tubes for 2.5 h daily over 13 days. Elevated plus-maze test (EPM) and forced swim test (FST) confirmed the presence of anxiety-like and depression-like behaviours respectively post-restraint. Brain changes were also detected by MR. The rs-fMRI data revealed hypoconnectivity within the salience and interoceptive networks and hyperconnectivity of several brain regions to the cingulate cortex. The 1 H-MRS data revealed decreased sensorimotor cortical glutamate, glutamine and combined glutamate-glutamine levels. Volumetric analysis of T2-weighted images revealed decreased hippocampal volume, which was also correlated with salience network connectivity. Depression-like behaviours were correlated with salience and interoceptive network connectivity, glutamate and combined glutamate-glutamine levels and hippocampal volume. Anxiety-like behaviours were correlated with both hippocampus connectivity and interoceptive network connectivity. The present findings identify significant changes in brain connectivity, neurometabolites and structure that are correlated with abnormal behaviour in CRS rats. 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.

Repeated restraint stress induced neurobehavioral and sexual hormone disorders in male rats

“…The CRS was carried out as previously described [14] with minor modifications. Briefly, during the CRS paradigm, stressed rats were transported from the colony room to a quiet room and restrained.…”

Synthesis of Benzoazepine Derivatives via Azide Rearrangement and Evaluation of Their Antianxiety Activities

“…Initially, stress was induced in rats by being immobilized in a plastic restrainer for 2 h/day for 14 days. The stress was evaluated using two methods including elevated plus maze (EPM) and open field test (OFT). , As compared to the control group, the 2-week stress induction showed anxiety-like behavior as demonstrated by both EPM and OFT. To establish a suitable dose of substances for antianxiety evaluation in rats, diazepam ( DZP ) and benzoazepine analogues ( 18c , 18h , 18j , 18n , and 18p ) were employed for the screening for the optimal dosage using EPM.…”