Investigating neuropsychological and reward-related deficits in a chronic corticosterone-induced model of depression. (January 2023) - Hales, Claire A.
Abstract: Chronic stress is a known risk factor for the development of major depression (MDD) and is commonly used to induce a depression-like phenotype in rodents. Similar phenotypic effects are also observed in rodents when treated chronically with the stress hormone corticosterone. In this study, we investigated the neuropsychological consequences of chronic corticosterone treatment in male rats using two translational rodent assays of affective bias, the judgement bias task (JBT) and affective bias test (ABT). We also used the reward learning assay (RLA) and sucrose preference test (SPT) to quantify reward-related behaviours. Negative biases in decision-making were observed in the chronic corticosterone-treated group but only when the treatment was given shortly before each behavioural session. The same dose of corticosterone, when given daily after completion of the behavioural session had no effects. Chronic corticosterone treatment did not potentiate negative affective biases in the ABT induced by either an acute pharmacological or stress manipulation but both reward learning and reward sensitivity were blunted. Analysis of the brain tissue from animals receiving chronic corticosterone found reduced hippocampal neurogenesis consistent with previous studies suggesting corticosterone-induced neurotrophic deficits. Taken together, these data suggest chronic corticosterone treatment induces neuropsychological effects related to changes in reward learning, memory and negative biases in decision making, but these decision-making biases depend on whether rewarding outcomes were experienced during the acute effects of the drug. These findings suggest an important interaction between psychological and biological factors resulting in negative biases in decision-making in this model. Highlights: Chronic corticosterone (CORT) treatment induced negative decision-making biases. Negative decision-making biases were dependent on treatment timing. Chronic CORT treatment caused impairments in reward learning and reward sensitivity. CORT treatment did not potentiate pharmacological or stress induced negative bias. Chronic CORT treatment reduced neurogenesis in the hippocampus.