Evaluation of the Wistar-Kyoto rat model of depression and the role of synaptic plasticity in depression and antidepressant response. 2019

Lily R Aleksandrova, and Yu Tian Wang, and Anthony G Phillips
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada; Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

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.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D009415 Nerve Net A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction. Neural Networks (Anatomic),Nerve Nets,Net, Nerve,Nets, Nerve,Network, Neural (Anatomic),Networks, Neural (Anatomic),Neural Network (Anatomic)
D009473 Neuronal Plasticity The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations. Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D011921 Rats, Inbred WKY A strain of Rattus norvegicus used as a normotensive control for the spontaneous hypertensive rats (SHR). Rats, Wistar Kyoto,Wistar Kyoto Rat,Rats, WKY,Inbred WKY Rat,Inbred WKY Rats,Kyoto Rat, Wistar,Rat, Inbred WKY,Rat, WKY,Rat, Wistar Kyoto,WKY Rat,WKY Rat, Inbred,WKY Rats,WKY Rats, Inbred,Wistar Kyoto Rats
D003865 Depressive Disorder, Major Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5) Depression, Involutional,Major Depressive Disorder,Melancholia, Involutional,Paraphrenia, Involutional,Psychosis, Involutional,Depressive Disorders, Major,Involutional Depression,Involutional Melancholia,Involutional Paraphrenia,Involutional Paraphrenias,Involutional Psychoses,Involutional Psychosis,Major Depressive Disorders,Paraphrenias, Involutional,Psychoses, Involutional
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000928 Antidepressive Agents Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems. Antidepressant,Antidepressant Drug,Antidepressant Medication,Antidepressants,Antidepressive Agent,Thymoanaleptic,Thymoanaleptics,Thymoleptic,Thymoleptics,Antidepressant Drugs,Agent, Antidepressive,Drug, Antidepressant,Medication, Antidepressant
D017397 Prefrontal Cortex The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin. Anterior Prefrontal Cortex,Brodmann Area 10,Brodmann Area 11,Brodmann Area 12,Brodmann Area 47,Brodmann's Area 10,Brodmann's Area 11,Brodmann's Area 12,Brodmann's Area 47,Pars Orbitalis,Frontal Sulcus,Gyrus Frontalis Inferior,Gyrus Frontalis Superior,Gyrus Orbitalis,Gyrus Rectus,Inferior Frontal Gyrus,Lateral Orbitofrontal Cortex,Marginal Gyrus,Medial Frontal Gyrus,Olfactory Sulci,Orbital Area,Orbital Cortex,Orbital Gyri,Orbitofrontal Cortex,Orbitofrontal Gyri,Orbitofrontal Gyrus,Orbitofrontal Region,Rectal Gyrus,Rectus Gyrus,Straight Gyrus,Subcallosal Area,Superior Frontal Convolution,Superior Frontal Gyrus,Ventral Medial Prefrontal Cortex,Ventromedial Prefrontal Cortex,Anterior Prefrontal Cortices,Area 10, Brodmann,Area 10, Brodmann's,Area 11, Brodmann,Area 11, Brodmann's,Area 12, Brodmann,Area 12, Brodmann's,Area 47, Brodmann,Area 47, Brodmann's,Area, Orbital,Area, Subcallosal,Brodmanns Area 10,Brodmanns Area 11,Brodmanns Area 12,Brodmanns Area 47,Convolution, Superior Frontal,Convolutions, Superior Frontal,Cortex, Anterior Prefrontal,Cortex, Lateral Orbitofrontal,Cortex, Orbital,Cortex, Orbitofrontal,Cortex, Prefrontal,Cortex, Ventromedial Prefrontal,Cortices, Ventromedial Prefrontal,Frontal Convolution, Superior,Frontal Gyrus, Inferior,Frontal Gyrus, Medial,Frontal Gyrus, Superior,Frontalis Superior, Gyrus,Gyrus, Inferior Frontal,Gyrus, Marginal,Gyrus, Medial Frontal,Gyrus, Orbital,Gyrus, Orbitofrontal,Gyrus, Rectal,Gyrus, Rectus,Gyrus, Straight,Gyrus, Superior Frontal,Inferior, Gyrus Frontalis,Lateral Orbitofrontal Cortices,Olfactory Sulcus,Orbital Areas,Orbital Cortices,Orbital Gyrus,Orbitalis, Pars,Orbitofrontal Cortex, Lateral,Orbitofrontal Cortices,Orbitofrontal Cortices, Lateral,Orbitofrontal Regions,Prefrontal Cortex, Anterior,Prefrontal Cortex, Ventromedial,Prefrontal Cortices, Anterior,Region, Orbitofrontal,Subcallosal Areas,Sulcus, Frontal,Superior Frontal Convolutions,Superior, Gyrus Frontalis,Ventromedial Prefrontal Cortices

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