Urine Scent Marking (USM): A Novel Test for Depressive-Like Behavior and a Predictor of Stress Resiliency in Mice

Lehmann, Michael L.; Geddes, Claire E.; Lee, Jennifer L.; Herkenham, Miles

doi:10.1371/journal.pone.0069822

Cited by 50 publications

(54 citation statements)

References 81 publications

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“…Scent‐marking requires no social experience (Lehmann et al . ; Novotny et al . ), whereas ultrasonic vocalizations require social experience with females and female scent exposure.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder

Kabitzke

Brunner

et al. 2017

Genes Brain and Behavior

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To expand, analyze and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3 model, hereafter Shank3/F, Jiang's Shank3 model, hereafter Shank3/J and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. This study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. We found that some but not all behaviors replicated published findings and those that did replicate, such as social behavior and overgrooming in Shank3 models, tended to be milder than reported elsewhere. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, only Shank3/F showed differences in sensory-gating. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.

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“…Scent‐marking requires no social experience (Lehmann et al . ; Novotny et al . ), whereas ultrasonic vocalizations require social experience with females and female scent exposure.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder

Kabitzke

Brunner

et al. 2017

Genes Brain and Behavior

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“…We should also note that another study in mice did not find a correlation between social rank assessed in the homecage and vulnerability to social defeat. However, at difference to Larrieu et al that exposed mice to a chronic social defeat immediately after group cohabitation, mice in the Lehmann et al study were 1) socially isolated during 2 weeks and 2) exposed to an acute social defeat stress. Such isolation procedure might have altered individuals’ predispositions and, the use of acute social defeat rather than CSDS might be not sufficient to produce susceptibility in dominant mice.…”

Section: Issues Related To How the Dominance–submissive Relationship mentioning

confidence: 94%

Stress‐Induced Depression: Is Social Rank a Predictive Risk Factor?

Larrieu

Sandi

2018

BioEssays

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An intriguing question in the field of stress is what makes an individual more likely to be susceptible or resilient to stress-induced depression. Predisposition to stress susceptibility is believed to be influenced by genetic factors and early adversity. However, beyond genetics and life experiences, recent evidence has highlighted social rank as a key determinant of susceptibility to stress, underscoring dominant individuals as the vulnerable ones. This evidence is in conflict with epidemiological, clinical, and animal work pointing at a link between social subordination and depression. Here, we review and analyze rodent protocols addressing the relevance of social rank to predict vulnerability to chronic social stress. We also discuss whether a specific social status (i.e., dominance or subordination) is the appropriate predictor of vulnerability to develop stress-induced depression or rather, the loss of social rank and resources.

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“…Fluoxetine (20 mg kg −1 day −1 ) or saline was administrated (i.p.) prior to and concurrent with CSDS for 21 days (Han, Lee, & Leem, ; Lehmann, Geddes, Lee, & Herkenham, ; Talbot et al, ). Twenty‐four hours after CSDS, C57 mice were examined with behavioral tests.…”

Section: Methodsmentioning

confidence: 99%

Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

et al. 2020

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Introduction A growing body of evidence suggests that stress is an important factor in depression, and pro‐inflammatory cytokines contribute to the occurrence and development of depression in both animal models and human patients. Toll‐like receptor 4 (TLR4) has been shown to be a key innate immune pattern recognition receptor involved in the regulation of stress responses and inflammation. However, the exact effects of TLR4 on depressive‐like behaviors induced by chronic social defeat stress (CSDS) are not known. Methods In this study, the effects of TLR4 on depressive‐like behaviors were investigated in an animal model of depression induced by CSDS. The depressive‐like behaviors were assessed by forced swimming test (FST), social interaction test (SIT), and light–dark box test (LDT). The protein expressions of TLR4 and tumor necrosis factor‐α (TNF‐α) in the hippocampus were measured using Western blotting. Results We found that CSDS increased TLR4 protein levels in the hippocampus and induced behavioral despair in FST, social avoidance in SIT, and anxiety‐like behavior in LDT. Fluoxetine normalized the increased expression of TLR4 and reversed behavioral despair, social avoidance, as well as anxiety‐like behavior induced by CSDS. However, directly blocking TLR4, by using either TLR4 inhibitor TAK‐242 or knockout of TLR4, only inhibited behavioral despair, but not social avoidance or anxiety‐like behavior induced by CSDS. Conclusions These results demonstrate a specific modulating role of TLR4 in behavioral despair induced by CSDS and suggest that TAK‐242 may be a beneficial treatment for patients with behavioral despair.

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Urine Scent Marking (USM): A Novel Test for Depressive-Like Behavior and a Predictor of Stress Resiliency in Mice

Cited by 50 publications

References 81 publications

Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder

Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder

Stress‐Induced Depression: Is Social Rank a Predictive Risk Factor?

Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

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