Cited by 115Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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

Aleksandrova, Lily R., Wang, Yu Tian, Phillips, Anthony G.·2019·Neuroscience & Biobehavioral Reviews

Abstract

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.

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Crossref · 10.1016/j.neubiorev.2019.07.007

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Authors
Aleksandrova, L. R., Wang, Y. T., & Phillips, A. G.
Affiliations
University of British Columbia (CA)
Corresponding author
  • Wang, Yu Tian
  • Phillips, Anthony G.
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
2019-10
Volume
105
Pages
1-23
ISSN
0149-7634 (ISSN-L)
OpenAlex
W2962912563
Cited by
114
References
284
Citations by year
2026: 12 · 2025: 22 · 2024: 18 · 2023: 18 · 2022: 19 · 2021: 12 · 2020: 12 · 2019: 1
FWCI
6.82
Type
journal article
Language
en
Update notices
erratum (2020-09-01)
Open access
closed
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Wistar-Kyoto rats, animal models of depression, major depressive disorder, synaptic plasticity, antidepressant response, stress vulnerability, stress tolerance, ketamine, hippocampus, prefrontal cortex, neuronal atrophy, neuronal connectivity, treatment-resistant depression
MeSH terms
Animals, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Disease Models, Animal, Hippocampus, Ketamine, Nerve Net, Neuronal Plasticity, Rats, Inbred WKY, Prefrontal Cortex, Rats

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