Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Sci Rep. 2021 Apr 27;11(1):9113. doi: 10.1038/s41598-021-88462-7.
Depression-associated cognitive impairments are among the most prevalent and persistent symptoms during remission from a depressive episode and a major risk factor for relapse. Consequently, development of antidepressant drugs, which also alleviate cognitive impairments, is vital. One such potential antidepressant is vortioxetine that has been postulated to exhibit both antidepressant and pro-cognitive effects. Hence, we tested vortioxetine for combined antidepressant and pro-cognitive effects in male Long-Evans rats exposed to the chronic mild stress (CMS) paradigm. This well-established CMS paradigm evokes cognitive deficits in addition to anhedonia, a core symptom of depression. Learning and memory performance was assessed in the translational touchscreen version of the paired-associates learning task. To identify the mechanistic underpinning of the neurobehavioural results, transcriptional profiling of genes involved in the stress response, neuronal plasticity and genes of broad relevance in neuropsychiatric pathologies were assessed. Vortioxetine substantially relieved the anhedonic-like state in the CMS rats and promoted acquisition of the cognitive test independent of hedonic phenotype, potentially due to an altered cognitive strategy. Minor alterations in gene expression profiling in prefrontal cortex and hippocampus were found. In summary, our findings suggest that vortioxetine exhibits an antidepressant effect as well as behavioural changes in a translational learning task.
抑郁相关的认知损伤是抑郁发作缓解后最常见和持续存在的症状之一，也是复发的主要危险因素。因此，开发既能缓解认知损伤又能抗抑郁的抗抑郁药物至关重要。文拉法辛就是这样一种有潜力的抗抑郁药，它被认为具有抗抑郁和促认知作用。因此，我们在慢性轻度应激（CMS）模型中测试了文拉法辛对雄性 Long-Evans 大鼠的抗抑郁和促认知作用。这种成熟的 CMS 模型除了引发快感缺失（抑郁症的核心症状）外，还会引发认知缺陷。在转化型触摸屏配对联想学习任务中评估学习和记忆表现。为了确定神经行为结果的机制基础，我们评估了应激反应、神经元可塑性以及神经精神病理学广泛相关基因中涉及的基因的转录谱。文拉法辛可显著缓解 CMS 大鼠的快感缺失样状态，并促进认知测试的获得，而与快感缺失表型无关，这可能是由于认知策略的改变。在前额叶皮层和海马体中发现了基因表达谱的微小变化。总之，我们的研究结果表明，文拉法辛在转化学习任务中表现出抗抑郁作用和行为改变。
