Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Kim, Sarah; Gacek, Stephanie A.; Mocchi, Madaline M.; Redei, Eva E.

doi:10.3389/fnbeh.2021.779036

Cited by 5 publications

(1 citation statement)

References 69 publications

(84 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stress during adolescence is thought to be a major contributor to psychopathology in adulthood [ 161 ]. In both WMI and WLI rats, a very mild single stress during early adolescence significantly decreases anxiety-like behavior, measured in the OFT, and increases social interaction and recognition in adult males compared to controls [ 162 ]. In contrast, no significant effects of early adolescent stress are observed in adult females of either strain in these behaviors.…”

Section: Selective Breeding: Wmi and Wli Substrainsmentioning

confidence: 99%

The Wistar Kyoto Rat: A Model of Depression Traits

Redei

Udell

Solberg‐Woods

et al. 2023

Self Cite

View full text Add to dashboard Cite

There is an ongoing debate about the value of animal research in psychiatry with valid lines of reasoning stating the limits of individual animal models compared to human psychiatric illnesses. Human depression is not a homogenous disorder; therefore, one cannot expect a single animal model to reflect depression heterogeneity. This limited review presents arguments that the Wistar Kyoto (WKY) rats show intrinsic depression traits. The phenotypes of WKY do not completely mirror those of human depression but clearly indicate characteristics that are common with it. WKYs present despair-like behavior, passive coping with stress, comorbid anxiety, and enhanced drug use compared to other routinely used inbred or outbred strains of rats. The commonly used tests identifying these phenotypes reflect exploratory, escape-oriented, and withdrawal-like behaviors. The WKYs consistently choose withdrawal or avoidance in novel environments and freezing behaviors in response to a challenge in these tests. The physiological response to a stressful environment is exaggerated in WKYs. Selective breeding generated two WKY substrains that are nearly isogenic but show clear behavioral differences, including that of depression-like behavior. WKY and its substrains may compare characteristics of subgroups of depressed individuals with social withdrawal, low energy, weight loss, sleep disturbances, and specific cognitive dysfunction. The genomes of the WKY and WKY substrains contain variations that impact the function of many genes identified in recent human genetic studies of depression. Thus, these strains of rats share characteristics of human depression at both phenotypic and genetic levels, making them a model of depression traits.

show abstract

Section: Selective Breeding: Wmi and Wli Substrainsmentioning

confidence: 99%

The Wistar Kyoto Rat: A Model of Depression Traits

Redei

Udell

Solberg‐Woods

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

Female Wistar Kyoto More Immobile rats with genetic stress hyper‐reactivity show enhanced contextual fear memory without deficit in extinction of fear

Harter,

Nemesh,

et al. 2024

Eur J of Neuroscience

View full text Add to dashboard Cite

The prevalence of post‐traumatic stress disorder (PTSD) is higher in females than males, but pre‐clinical models are established almost exclusively in males. This study is aimed to investigate the stress‐enhanced fear learning model of PTSD in females. The model mirrors PTSD symptomology in males, whereby prior stress leads to extinction resistant exaggerated contextual fear memory. As stress reactivity is highly relevant to the study and risk for PTSD, females of the stress hyper‐reactive Wistar Kyoto More Immobile (WMI) and its nearly isogenic control the Wistar Kyoto Less Immobile (WLI) strains were employed. Prior studies have shown WMI females presenting unchanged or enhanced fear memory in the stress‐enhanced fear learning paradigm compared WLIs. The present study confirmed the enhanced fear memory following contextual fear conditioning in WMIs compared to WLI females, but this increased fear memory was neither exaggerated by prior stress nor showed extinction deficit. The novel stressor of a glucose challenge test resulted in subtle strain‐ and prior stress‐induced differences in plasma glucose responses. However, fasting plasma corticosterone levels were lower, and rose slower in response to glucose challenge in WMI females, suggesting a PTSD‐like dysfunctional stress response. Hippocampal expressions of genes relevant to both learning and memory and the stress response were decreased in stressed WMIs compared to WLI females, further suggesting a marked dysregulation in stress‐related functions like in PTSD. Thus, although WMI females do not show extinction‐resistant enhanced fear memory, they do present other characteristics that are relevant to PTSD in women.

show abstract

Stress enhances aggression in male rats with genetic stress hyper‐reactivity

Harter,

Kim,

Yamazaki

et al. 2024

Genes Brain and Behavior

View full text Add to dashboard Cite

The current study investigated stress‐induced aggressive behavior in the resident‐intruder test in males of the genetically stress hyper‐reactive Wistar Kyoto More Immobile (WMI), and the nearly isogenic, control Wistar Kyoto Less Immobile (WLI) strains. Tests were carried out against same‐age intruders during adolescence, and same‐age and juvenile intruders in adulthood. In adolescence and adulthood, prior acute restraint stress decreased social interactions and decreased aggressive behaviors of adolescents and adult WLIs. However, prior stress precipitated aggression in the adult WMI males toward both same‐age, and juvenile intruders compared with control WMIs and WLIs. Trunk blood levels of testosterone and androstenedione increased in stressed WLIs, but not in WMIs, suggesting no direct role of androgens in the increased aggression of WMIs. Expressions of aggression‐relevant genes showed patterns commensurate with being causative in aggressive behavior. The methyl‐CpG binding protein 2 was lower in the frontal cortex of control WMIs, and in the amygdala of stressed WMIs compared with their respective WLIs. Frontal cortex expression of vasopressin receptor 1a and serotonin transporter increased, solely in WMI males after stress. As behaviors were the same toward same‐age and non‐threatening juvenile intruders, the stress‐induced increase in confrontational behavior of the adult WMI male was not because of enhanced fear or anxiety. These results suggest that genetic stress hyper‐reactivity is a risk factor for stress‐induced increases in aggression in males. Additionally, as known aggression‐related genes showed expression patterns paralleling aggressive behavior, this model system could identify novel molecular pathways leading to stress‐enhanced aggression.

show abstract

Sex-Specific Behavioral Response to Early Adolescent Stress in the Genetically More Stress-Reactive Wistar Kyoto More Immobile, and Its Nearly Isogenic Wistar Kyoto Less Immobile Control Strain

Cited by 5 publications

References 69 publications

The Wistar Kyoto Rat: A Model of Depression Traits

The Wistar Kyoto Rat: A Model of Depression Traits

Female Wistar Kyoto More Immobile rats with genetic stress hyper‐reactivity show enhanced contextual fear memory without deficit in extinction of fear

Stress enhances aggression in male rats with genetic stress hyper‐reactivity

Contact Info

Product

Resources

About