Evaluation of the Wistar-Kyoto rat model of depression and the role of synaptic plasticity in depression and antidepressant response

Neurosci Biobehav Rev. 2019 Oct;105:1-23. doi: 10.1016/j.neubiorev.2019.07.007. Epub 2019 Jul 20.


In order to expand the prospects of developing novel antidepressants for treatment-resistant populations, animal models should incorporate not only various stress-induced behavioural, neurochemical and endocrine parallels to major depressive disorder (MDD), but also aspects of heightened stress susceptibility and resistance to conventional drugs. This review focuses on the available literature supporting the Wistar-Kyoto (WKY) rat as a model of endogenous stress susceptibility and depression, and the role of synaptic plasticity in depression and antidepressant response in the context of this model. Accumulating evidence implicates a dysregulation of synaptic plasticity in the etiology of depression, leading to synaptic weakening and neuronal atrophy in vulnerable brain regions (hippocampus, prefrontal cortex). Furthermore, novel antidepressant treatments, particularly ketamine, may reverse the stress-induced loss of connectivity in these key neural circuits by engaging synaptic plasticity processes to "reset the system". Incorporating synaptic plasticity into the current framework of antidepressant action may serve to bridge understanding of an antidepressant's molecular and cellular effects with those related to regional structural plasticity and neural circuit functioning.

Keywords: Antidepressant; Depression susceptibility; Hippocampus; Ketamine; LTD; LTP; Model of depression; Prefrontal cortex; Synaptic plasticity; Treatment resistance; Wistar-Kyoto rat.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / metabolism
  • Depressive Disorder, Major* / physiopathology
  • Disease Models, Animal*
  • Hippocampus* / drug effects
  • Hippocampus* / physiopathology
  • Ketamine / pharmacology*
  • Nerve Net* / drug effects
  • Nerve Net* / physiopathology
  • Neuronal Plasticity* / drug effects
  • Neuronal Plasticity* / physiology
  • Prefrontal Cortex* / drug effects
  • Prefrontal Cortex* / physiopathology
  • Rats
  • Rats, Inbred WKY*


  • Antidepressive Agents
  • Ketamine

Grant support