The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

Koolhaas, Jaap M.; Coppens, Caroline M.; Boer, Sietse F. de; Buwalda, Bauke; Meerlo, Peter; Timmermans, P.J.A.

doi:10.3791/4367-v

Cited by 45 publications

(56 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The copyright holder for this preprint this version posted March 1, 2023. ; https://doi.org/10.1101/2023.02. 28.530477 doi: bioRxiv preprint…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Naik

Munyeshyaka

et al. 2023

Preprint

View full text Add to dashboard Cite

BackgroundIrritability, which can be defined as proneness to anger that can reach a pathological extent, is one of the most common reasons youth present for psychiatric evaluation and care. Aberrant responses to frustrative non-reward (FNR, the response to omission of an expected reward) are central to the pathophysiology of irritability. FNR is a cross-species RDoC construct. The development of preclinical FNR models could advance mechanistic studies of the important, and relatively understudied, clinical phenomenon of irritability.MethodsWe used FNR, a translational construct across species, as a conceptual framework for a novel behavioral paradigm (Alternate Poking Reward Omission, APRO) in mice. After APRO, mice were examined with a battery of behavioral tests to determine the effects of frustration. Also, whole brain imaging of c-Fos expression was used to identify brain regions activated by FNR.ResultsMice, regardless of sex, increased locomotion, and aggression towards conspecifics after APRO. There was no change in anxiety-like, depression-like, or non-aggressive social behaviors. APRO causes activation of 13 regions in the prelimbic, ACC, hippocampus, dorsal thalamus, cuneiform nucleus, pons, and pallidum areas, and shifts the brain network towards a more global processing mode.ConclusionOur novel FNR paradigm produces a frustration effect and alters brain processing in ways resembling the symptoms and brain network reconfiguration observed in youth with severe irritability. The novel behavioral paradigm and brain regions identified to be selectively activated by it lay the groundwork for further mechanistic studies of frustration and irritability in rodents.

show abstract

“…The copyright holder for this preprint this version posted March 1, 2023. ; https://doi.org/10.1101/2023.02. 28.530477 doi: bioRxiv preprint…”

Section: Discussionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 1, 2023. ; https://doi.org/10.1101/2023.02. 28.530477 doi: bioRxiv preprint the task, FNR was introduced by reward omission (10,13) . Amsel demonstrated that FNR invigorates behavior as indicated by faster running and increased resistance to extinction.…”

Section: Introductionmentioning

confidence: 99%

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Naik

Munyeshyaka

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In social defeat models using rats, aggression and territorial dominance of residents toward intruder males can be established by pair-housing with a ligatured female [28]. In this way, the female kept hormonally intact and will be commonly receptive without becoming pregnant and developing maternal aggression [29]. The intruders were defeated and forced into subordination including attacks, bites, and threats by the residents for 10 min after the first attack.…”

Section: Methodsmentioning

confidence: 99%

“…It is noteworthy that the physical injury in a nonviolent social defeat confrontation includes biting as brief nipping of the skin mainly at the back and flanks of the intruder with thick and tough skin, which leaves behind small imprints of the incisors and does not require any veterinary care [30]. Therefore, the confrontation should be terminated earlier upon the resident that shows signs of violence causing bite wounds at vulnerable body parts (belly, throat, and paws) and the violent resident should be excluded from the experiment [29]. Right after the physical defeat session, the intruders were separated from the residents with a perforated transparent partition which allowed psychogenic contacts to the resident without physical harm for 1 h. The daily defeat was performed during the dark phase (the main activity phase) with different resident rats to minimize repeated encounters throughout the experiment.…”

Section: Methodsmentioning

confidence: 99%

Investigating the Effects of Maternal Separation on Hypothalamic-Pituitary-Adrenal Axis and Glucose Homeostasis under Chronic Social Defeat Stress in Young Adult Male Rat Offspring

et al. 2022

View full text Add to dashboard Cite

Introduction: Given the suggested metabolic regulatory effects of stress-responsive genes and based on the impacts of early life stress on HPA axis development, this study aimed to characterize the maternal separation (MS) impact on the communication between glucose metabolism and HPA axis dysregulations under chronic social defeat stress (CSDS). Methods: During the first two weeks of life, male Wistar rats were either exposed to MS or left undisturbed with their mothers (Std). Starting on postnatal day 50, the animals of each group were either left undisturbed in the standard group housing (Con) or underwent CSDS for three weeks. There were four groups (n=10/group): Std-Con, Ms-Con, Std-CSDS, and MS-CSDS. Results: Early-and/or adult life adversity reduced β-cell number, muscular FK506-binding protein 51 (FKBP51) content, and BMI in adulthood. The reduction of β-cell number and BMI in the MS-CSDS rats were more profound than MS-Con group. CSDS either alone or in combination with MS reduced locomotor activity and increased and decreased corticotropin-releasing factor type 1 receptor (CRFR1) content respectively in hypothalamus and pancreas. Although, under CSDS, MS intensified HPA axis overactivity and reduced isolated islets’ insulin secretion, it could promote resilience to depression symptoms. No differences were observed in hypothalamic Fkbp5 gene DNA methylation and glucose tolerance among groups. Conclusion: MS exacerbated HPA axis overactivity and the endocrine pancreas dysfunctions under CSDS. The intensified corticosterone secretion and the diminished content of pancreatic CRFR1 protein could be involved in the reduced β-cell number and islets’ insulin secretion under CSDS. The decreased muscular FKBP51 protein content might be a homeostatic response to slow down insulin resistance development under chronic stress.

show abstract

“…Resident-intruder test -To evaluate aggressive behavior, male mice were subjected to the resident-intruder paradigm [94]. Experimental animals (residents) were housed in transparent cages (36 × 25 × 25 cm) singly for 24 h before the test to develop territoriality.…”

Section: Behavioral Analysesmentioning

confidence: 99%

S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis

et al. 2021

View full text Add to dashboard Cite

Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD. Interestingly, it has been shown that increased S100B levels affect zinc homeostasis in vitro. Thus, here, we investigated the influence of increased S100B levels in vitro and in vivo during pregnancy in mice regarding zinc availability, the zinc-sensitive SHANK protein networks associated with ASD, and behavioral outcomes. We observed that S100B affects the synaptic SHANK2 and SHANK3 levels in a zinc-dependent manner, especially early in neuronal development. Animals exposed to high S100B levels in utero similarly show reduced levels of free zinc and SHANK2 in the brain. On the behavioral level, these mice display hyperactivity, increased stereotypic and abnormal social behaviors, and cognitive impairment. Pro-inflammatory factors and zinc-signaling alterations converge on the synaptic level revealing a common pathomechanism that may mechanistically explain a large share of ASD cases.

show abstract

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

Cited by 45 publications

References 0 publications

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration

Investigating the Effects of Maternal Separation on Hypothalamic-Pituitary-Adrenal Axis and Glucose Homeostasis under Chronic Social Defeat Stress in Young Adult Male Rat Offspring

S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis

Contact Info

Product

Resources

About