The Wistar-Kyoto rat model of endogenous depression: A tool for exploring treatment resistance with an urgent need to focus on sex differences.

Progress in Neuro-psychopharmacology & Biological Psychiatry
Samuel J MillardKelly A Newell

Abstract

Major depressive disorder (MDD) is one of the leading causes of years lived with disability and contributor to the burden of disease worldwide. The incidence of MDD has increased by ~20% in the last decade. Currently antidepressant drugs such as the popular selective serotonin reuptake inhibitors (SSRIs) are the leading form of pharmaceutical intervention for the treatment of MDD. SSRIs however, are inefficient in ameliorating depressive symptoms in ~50% of patients and exhibit a prolonged latency of efficacy. Due to the burden of disease, there is an increasing need to understand the neurobiology underpinning MDD and to discover effective treatment strategies. Endogenous models of MDD, such as the Wistar-Kyoto (WKY) rat provide a valuable tool for investigating the pathophysiology of MDD. The WKY rat displays behavioural and neurobiological phenotypes similar to that observed in clinical cases of MDD, as well as resistance to common antidepressants. Specifically, the WKY strain exhibits increased anxiety- and depressive-like behaviours, as well as alterations in Hypothalamic Pituitary Adrenal (HPA) axis, serotonergic, dopaminergic and neurotrophic systems with emerging studies suggesting an involvement of neuroinflammation. Mo...Continue Reading

Citations

Dec 29, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Chien-Han Lai
May 19, 2021·Pharmacological Reports : PR·Jan Detka, Katarzyna Głombik
May 25, 2021·Neuroscience and Biobehavioral Reviews·Samara J BrownKelly A Newell

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