The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Burstein, Or; Doron, Ravid

doi:10.3791/58184

Cited by 39 publications

(29 citation statements)

References 117 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The body weight and sucrose preference were monitored weekly during the protocol ( Figure 1A). As expected, the CUMS group showed progressive decreases in body weight and sucrose preference ( Figures 1B,C), which are the typical signs of depression (Burstein and Doron, 2018). Furthermore, we performed the forced swim test (FST) and tail suspension test (TST) to assess the depressive state.…”

Section: Experimental Workflow and Depression-like States Induced By supporting

confidence: 53%

A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics

Xiao

Luo

Yang

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Depression is a common affective disorder characterized by significant and persistent low mood. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to have a rapid and durable antidepressant effect, but the mechanisms are unclear. Protein phosphorylation is a post-translational modification that plays a crucial role in cell signaling. Thus, we present a phosphoproteomics approach to investigate the mechanisms underlying stress-induced depression and the rapid antidepressant effect of ketamine in mice. We analyzed the phosphoprotein changes induced by chronic unpredictable mild stress (CUMS) and ketamine treatment in two known mood control centers, the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). We initially obtained >8,000 phosphorylation sites. Quantitation revealed 3,988 sites from the mPFC and 3,196 sites from the NAc. Further analysis revealed that changes in synaptic transmission-related signaling are a common feature. Notably, CUMS-induced changes were reversed by ketamine treatment, as shown by the analysis of commonly altered sites. Ketamine also induced specific changes, such as alterations in synapse organization, synaptic transmission, and enzyme binding. Collectively, our findings establish a signaling framework for stress-induced depression and the rapid antidepressant effect of ketamine.

show abstract

Section: Experimental Workflow and Depression-like States Induced By supporting

confidence: 53%

A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics

Xiao

Luo

Yang

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Repeated physical restraint in a conical tube or similar restraining device is a popular paradigm (Kim and Han, 2006). To avoid potential habituation to a single stressor over an extensive period of time, the unpredictable chronic mild stress procedure [UCMS or CUMS, with variations including chronic unpredictable stress (CUS or UCS), chronic mild stress (CMS), and chronic variable stress (CVS)] subjects rodents to several weeks of various stressors, such as noise, restraint, bedding deprivation, and light cycle disruption (Willner, 1997 and 2017; Burstein and Doron, 2018). While this protocol is widely used, it is quite labor intensive and some strains of mice, including the commonly used C57BL/6 strain, can be resistant to the effects of UCMS unless the duration of the protocol is greatly extended (Monteiro et al, 2015).…”

mentioning

confidence: 99%

Multiple Simultaneous Acute Stresses in Mice: Single or Repeated Induction

et al. 2020

View full text Add to dashboard Cite

Stress is crucial to the survival of an organism, but excessive stress can lead to psychological disorders including depression, anxiety, substance abuse, and suicidality. The prevailing notion is that chronic stress promotes adverse outcomes on brain and body health, whereas acute stressors are generally benign. Notably, acute events such mass shootings or natural disasters are now emerging as significant sources of cognitive and emotional problems including post-traumatic stress disorder (PTSD). These events are characterized by the simultaneous occurrence of physical, emotional, and social stresses, which last minutes to hours. Hence, there is a need to model such multiple concurrent acute stresses (MAS) to uncover the mechanisms by which they lead to profound adverse outcomes. The MAS paradigm described here involves simultaneously exposing a rodent to several different stressors including restraint, crowding, and jostling alongside peers in a brightly lit and very noisy environment. Moreover, the MAS paradigm can be used once or imposed repeatedly to emulate complex, repeated modern life stresses, advancing our mechanistic understanding of consequent mental and cognitive impairments.

show abstract

“…Consumptive behavior during the sucrose preference test has been the most frequently used approach to infer potential impairments in hedonic response in several animal models of depression (e.g., unpredictable chronic mild stress, olfactory bulbectomy, social defeat, as evidenced by Romeas et al, 2009;Burstein and Doron, 2018;Iñiguez et al, 2018;Antoniuk et al, 2019). While the present study indicated the presence of decreased consumptive behavior of sucrose solution in WKY rats, as indexed by the total amount of solution ingested, a potential confound arises from the fact that WKY rats were of lower overall bodyweight than their age-matched Wistar counterparts.…”

Section: Discussionmentioning

confidence: 99%

Wistar Kyoto Rats Display Anhedonia In Consumption but Retain Some Sensitivity to the Anticipation of Palatable Solutions

Wright

Gilmour

Dwyer

2020

Front. Behav. Neurosci.

View full text Add to dashboard Cite

The Wistar Kyoto (WKY) rat has been proposed as a model of depression-like symptoms. However, anhedonia-a reduction in the response to normatively rewarding events-as a central depression symptom has yet to be fully assessed in this model. We compared WKY rats and Wistar controls, with stress-susceptibility examined by applying mild unpredictable stress to a subset of each group. Anhedonia-like behavior was assessed using microstructural analysis of licking behavior, where mean lick cluster size reflects hedonic responses. This was combined with tests of anticipatory contrast, where the consumption of a moderately palatable solution (4% sucrose) is suppressed in anticipation of a more palatable solution (32% sucrose). WKY rats displayed greatly attenuated hedonic reactions to sucrose overall, although their reactions retained some sensitivity to differences in sucrose concentration. They displayed normal reductions in consumption in anticipatory contrast, although the effect of contrast on hedonic reactions was greatly blunted. Mild stress produced overall reductions in sucrose consumption, but this was not exacerbated in WKY rats. Moreover, mild stress did not affect hedonic reactions or the effects of contrast. These results confirm that the WKY substrain expresses a direct behavioral analog of anhedonia, which may have utility for increasing mechanistic understanding of depression symptoms.

show abstract

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Cited by 39 publications

References 117 publications

A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics

A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics

Multiple Simultaneous Acute Stresses in Mice: Single or Repeated Induction

Wistar Kyoto Rats Display Anhedonia In Consumption but Retain Some Sensitivity to the Anticipation of Palatable Solutions

Contact Info

Product

Resources

About