Genetic stress-reactivity, sex, and conditioning intensity affect stress-enhanced fear learning

Przybyl, K.J.; Jenz, Sophia T; Lim, Patrick H.; Ji, Ming; Wert, Stephanie L.; Luo, Wendy; Gacek, Stephanie A.; Schaack, A.K.; Redei, Eva E.

doi:10.1016/j.nlm.2021.107523

Cited by 5 publications

(4 citation statements)

References 63 publications

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“…Furthermore, SEFLsusceptible rats showed impaired extinction learning and impaired extinction memory retention, compared to SEFL-resilient rats with the same massed shock experience. Our finding that the SEFLsusceptible phenotype can be observed in group-housed rats extends a previous report that pairhousing animals does not protect against the development of the SEFL phenotype 28 and a recent report that group-housed animals are susceptible to a restraint-stress-based SEFL procedure 33 . Thus, group housing appears to be a potential refinement to the SEFL procedure.…”

Section: Behavioural Changes Associated With Sefl-susceptibilitysupporting

confidence: 89%

“…One limitation of the present research is that only male rats were studied. Although a recent study 18 showed no sex differences in susceptibility to the SEFL phenotype when a massed shock session was used as a prior stressor, there were differences in the behaviour of males and females when restraint stress was used to induce SEFL 33 . Differences in the expression of fear behaviour have been reported between males and females 35 , and the oestrus cycle may also influence fear behaviour 36 .…”

Section: Behavioural Changes Associated With Sefl-susceptibilitymentioning

confidence: 85%

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Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: a behavioral and molecular analysis

et al. 2022

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Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and the development of new treatment approaches. Analogue trauma procedures in animals, such as the stress-enhanced fear learning (SEFL) procedure, can be used to produce behavioural and neurobiological changes that have validity in modelling PTSD.However, by necessity the modelling of PTSD in animals requires causing potential pain and suffering to the animals. Consistent with the '3Rs' (reduction, refinement, replacement) of animal research, this study aimed to determine whether the SEFL procedure can be refined to reduce potential animal pain and suffering while retaining the same behavioural and neurobiological changes. Here we showed that PTSD-relevant changes could be produced in both behaviour and the brain of rats that were group-rather than single-housed and that received lower magnitude electric shocks in the 'trauma analogue' session. We also varied the number of shock exposures in the trauma analogue session, finding SEFL-susceptible and SEFL-resilient populations at all levels of shock exposure, but with greater levels of shock increasing the proportion of rats showing the SEFL-susceptible phenotype. These data demonstrate that the SEFL procedure can be used as an animal analogue of PTSD with reduced potential pain and suffering to the animals, and that variations in the procedure could be used to generate specific proportions of SEFL-susceptible and SEFL-resilient animals in future studies.

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Section: Behavioural Changes Associated With Sefl-susceptibilitysupporting

confidence: 89%

Section: Behavioural Changes Associated With Sefl-susceptibilitymentioning

confidence: 85%

Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: a behavioral and molecular analysis

et al. 2022

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“…WMI males show exaggerated fear memory in the contextual fear-conditioning (CFC) paradigm after prior stress, whereas the control WLI males do not. In contrast, female WLIs show this enhanced fear memory, but female WMIs do not [ 169 , 170 ]. The main findings indicate that the measures of the stress response, percent time spent freezing at the acquisition of the fear conditioning, and the measure of fear memory, which is freezing at recall, differ between these strains in both with and without prior stress conditions.…”

Section: Selective Breeding: Wmi and Wli Substrainsmentioning

confidence: 99%

“…The main findings indicate that the measures of the stress response, percent time spent freezing at the acquisition of the fear conditioning, and the measure of fear memory, which is freezing at recall, differ between these strains in both with and without prior stress conditions. The significant correlations between percent freezing at acquisition and at recall suggest that fear memory differences represent a true phenotype related to the stress-reactivity/passive coping or depressive behavior differences between the strains [ 169 ].…”

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

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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.

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Amentoflavone impairs the reconsolidated fear memories through inhibition of ERK pathway

Sun

Xie

et al. 2022

Biochemical and Biophysical Research Communications

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Genetic stress-reactivity, sex, and conditioning intensity affect stress-enhanced fear learning

Cited by 5 publications

References 63 publications

Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: a behavioral and molecular analysis

Refinement of the stress-enhanced fear learning model of post-traumatic stress disorder: a behavioral and molecular analysis

The Wistar Kyoto Rat: A Model of Depression Traits

Amentoflavone impairs the reconsolidated fear memories through inhibition of ERK pathway

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