Benefits of animal models to understand the pathophysiology of depressive disorders

Abstract

Major depressive disorder (MDD) is a potentially life-threatening mental disorder imposing severe social and economic burden worldwide. Despite the existence of effective antidepressant treatment strategies the exact pathophysiology of the disease is still unknown. Large number of animal models of MDD have been developed over the years, but all of them suffer from significant shortcomings. Despite their limitations these models have been extensively used in academic research and drug development. The aim of this review is to highlight the benefits of animal models of MDD. We focus here on recent experimental data where animal models were used to examine current theories of this complex disease. We argue, that despite their evident imperfections, these models provide invaluable help to understand cellular and molecular mechanisms contributing to the development of MDD. Furthermore, animal models are utilized in research to find clinically useful biomarkers. We discuss recent neuroimaging and microRNA studies since these investigations yielded promising candidates for biomarkers. Finally, we briefly summarize recent progresses in drug development, i.e. the FDA approval of two novel antidepressant drugs: S-ketamine and brexanolone (allopregnanolone). Deeper understanding of the exact molecular and cellular mechanisms of action responsible for the antidepressant efficacy of these rapid acting drugs could aid us to design further compounds with similar effectiveness, but less side effects. Animal studies are likely to provide valuable help in this endeavor.

Keywords: Drug development; Major depressive disorder; Micro RNA; Neuroimaging; Neuroplasticity; Stress.