University of Bristol, School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University Walk, Bristol BS8 1TD, UK; Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
University of Bristol, School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences, University Walk, Bristol BS8 1TD, UK.
Psychoneuroendocrinology. 2023 Jan;147:105953. doi: 10.1016/j.psyneuen.2022.105953. Epub 2022 Oct 19.
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.
慢性应激是导致重度抑郁症（MDD）发展的已知风险因素，通常用于在啮齿动物中诱导类似抑郁的表型。当用应激激素皮质酮慢性治疗啮齿动物时，也会观察到类似的表型效应。在这项研究中，我们使用两种翻译啮齿动物情感偏见测定法，即判断偏差任务（JBT）和情感偏差测试（ABT），研究了慢性皮质酮处理对雄性大鼠的神经心理学后果。我们还使用奖励学习测定法（RLA）和蔗糖偏好测试（SPT）来量化与奖励相关的行为。在慢性皮质酮处理组中观察到决策中的负性偏差，但仅在行为会议前不久给予治疗时才观察到。相同剂量的皮质酮，在完成行为会议后每天给予时，没有效果。慢性皮质酮处理不会增强 ABT 诱导的急性药理学或应激操作引起的负性情感偏见，但均削弱了奖励学习和奖励敏感性。对接受慢性皮质酮治疗的动物的脑组织进行分析发现，海马神经发生减少，与先前表明皮质酮诱导的神经营养缺陷的研究一致。总之，这些数据表明，慢性皮质酮处理会引起与奖励学习、记忆和决策中的负性偏差相关的神经心理学效应，但这些决策偏差取决于药物的急性作用期间是否经历了令人愉悦的结果。这些发现表明，在这种模型中，心理和生物学因素之间存在重要的相互作用，导致决策中的负性偏差。
