Source Paper
Source Paper
Journal of Neuroscience • 2011
Psychosocial stress is associated with altered immune function and development of psychological disorders including anxiety and depression. Here we show that repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner. Repeated social defeat also significantly increased the number of CD11b + /CD45 high /Ly6C high macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86) after social defeat. Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus. Moreover, mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]. The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist. Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice. Last, repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1. These findings indicate that repeated social defeat-induced anxiety-like behavior and enhanced reactivity of microglia was dependent on activation of β-adrenergic and IL-1 receptors.
Objective: To determine if β-adrenergic receptor antagonism with propranolol prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat stress
This is a Pharmacological β-Adrenergic Receptor Antagonism protocol using mouse as the model organism. The procedure involves 9 procedural steps, 1 equipment items, 2 materials. Extracted from a 2011 paper published in Journal of Neuroscience.
Model and subjects
mouse • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text
Study window
Estimated timing pending
Core workflow
Repeated Social Defeat Stress Protocol • Propranolol Administration • Anxiety-Like Behavior Assessment
Primary readouts
Key equipment and reagents
Verified items
0
Direct vendor links
0
Use this page as an execution guide, then fall back to the source paper whenever you need exact exclusions, dosing details, or assay-specific caveats.
Confirm first
Use the page like this
Start here. The step list is optimized for running the experiment, with direct vendor links available inline when you need to source a cited item.
Mice were subjected to repeated social defeat stress to induce anxiety-like behavior and immune activation
Note: This stress paradigm increased c-Fos staining in brain regions associated with fear and threat appraisal
“repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Propranolol was administered to block β-adrenergic receptors during or after social defeat stress
Note: Propranolol prevented stress-dependent changes in microglia and macrophages
“The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist”
Behavioral testing was conducted to measure anxiety-like responses following social defeat with or without propranolol treatment
Note: Anxiety-like behavior was dependent on β-adrenergic receptor activation
“promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner”
Brain tissue was collected and processed for c-Fos immunostaining to assess neuronal activation in fear and threat appraisal regions
Note: c-Fos staining was increased in brain regions associated with fear and threat appraisal after social defeat
“repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal”
Brain tissue was analyzed by flow cytometry to quantify CD11b+/CD45high/Ly6Chigh macrophages and assess inflammatory markers on microglia and macrophages
Note: Markers assessed included CD14, CD86, and TLR4 on microglia and macrophages
“Repeated social defeat also significantly increased the number of CD11b+/CD45high/Ly6Chigh macrophages that trafficked to the brain. In addition, several inflammatory markers were increased on the surface of microglia (CD14, CD86, and TLR4) and macrophages (CD14 and CD86)”
Brain tissue sections from medial amygdala, prefrontal cortex, and hippocampus were examined for microglial morphology
Note: Deramified (activated) microglia were increased in these brain regions after social defeat
“Repeated social defeat also increased the presence of deramified microglia in the medial amygdala, prefrontal cortex, and hippocampus”
mRNA was extracted from microglia and analyzed for expression of inflammatory cytokines and glucocorticoid-responsive genes
Note: Interleukin-1β levels were increased while GILZ and FKBP51 levels were reduced after social defeat
“mRNA analysis of microglia indicated that repeated social defeat increased levels of interleukin (IL)-1β and reduced levels of glucocorticoid responsive genes [glucocorticoid-induced leucine zipper (GILZ) and FK506 binding protein-51 (FKBP51)]”
Microglia were isolated from socially defeated and control mice, cultured ex vivo, and stimulated with lipopolysaccharide
Note: Microglia from defeated mice produced higher levels of IL-6, TNF-α, and MCP-1 compared to controls
“Microglia isolated from socially defeated mice and cultured ex vivo produced markedly higher levels of IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 after stimulation with lipopolysaccharide compared with microglia from control mice”
IL-1 receptor type-1-deficient mice were subjected to repeated social defeat to assess the role of IL-1 signaling
Note: Social defeat increased c-Fos activation but did not promote anxiety-like behavior or microglia activation in IL-1R1-deficient mice
“repeated social defeat increased c-Fos activation in IL-1 receptor type-1-deficient mice, but did not promote anxiety-like behavior or microglia activation in the absence of functional IL-1 receptor type-1”
This section explains what the experiment is doing, which readouts matter, what the data artifacts usually look like, and how the analysis should flow from raw capture to reported result.
To determine if β-adrenergic receptor antagonism with propranolol prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat stress
Objective
To determine if β-adrenergic receptor antagonism with propranolol prevents anxiety-like behavior and microglial reactivity induced by repeated social defeat stress
Subjects
From papermouse • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text • Not explicitly stated in provided text
Sample count
From paperNot explicitly stated in provided text
Cohort notes
From paperIL-1 receptor type-1-deficient mice were used in some experiments
Repeated Social Defeat Stress Protocol (Not explicitly stated in provided text)
Propranolol Administration (Not explicitly stated in provided text)
Anxiety-Like Behavior Assessment (Not explicitly stated in provided text)
Brain Tissue Collection and c-Fos Staining (Not explicitly stated in provided text)
Anxiety-like behavior
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
C-Fos staining in brain regions associated with fear and threat appraisal
From paperNot explicitly detailed in provided text
Artifact type
Representative image panels with region or marker comparisons
Comparison focus
Compare staining intensity, structure, or cell counts across matched conditions
Number of CD11b+/CD45high/Ly6Chigh macrophages in brain
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperNot explicitly detailed in provided text
Artifact type
Endpoint measurements summarized by group or timepoint
Comparison focus
Compare endpoint magnitude between groups, timepoints, or both
Anxiety-like behavior
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
C-Fos staining in brain regions associated with fear and threat appraisal
From paperRaw artifact
Field or section images captured from matched samples
Processed artifact
Selected representative panels with quantified intensity, counts, or area measurements
Final reported form
Per-group imaging summaries with representative figures and quantified endpoints
Number of CD11b+/CD45high/Ly6Chigh macrophages in brain
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Inflammatory markers on microglia surface (CD14, CD86, TLR4)
From paperRaw artifact
Per-sample or per-animal endpoint measurements collected during the experiment
Processed artifact
Structured table with cleaned measurements ready for comparison
Final reported form
Summary statistics and between-group or across-timepoint comparisons
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
Preprocessing / cleaning
Not explicitly detailed in provided text
Scoring or quantification
Quantify the primary readouts for this experiment: Anxiety-like behavior; C-Fos staining in brain regions associated with fear and threat appraisal; Number of CD11b+/CD45high/Ly6Chigh macrophages in brain; Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Statistical comparison
Statistical method not yet structured for this page.
Reporting output
Report representative outputs alongside summary comparisons for Anxiety-like behavior, C-Fos staining in brain regions associated with fear and threat appraisal, Number of CD11b+/CD45high/Ly6Chigh macrophages in brain, Inflammatory markers on microglia surface (CD14, CD86, TLR4).
Source links and direct wording from the methods section for validation and deeper review.
Citation
Eric S. Wohleb et al. (2011). β-Adrenergic Receptor Antagonism Prevents Anxiety-Like Behavior and Microglial Reactivity Induced by Repeated Social Defeat. Journal of Neuroscience
Repeated Social Defeat Stress Protocol • Protocol step
“repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal and promoted anxiety-like behavior”
Propranolol Administration • Protocol step
“The stress-dependent changes in microglia and macrophages were prevented by propranolol, a β-adrenergic receptor antagonist”
Anxiety-Like Behavior Assessment • Protocol step
“promoted anxiety-like behavior in a β-adrenergic receptor-dependent manner”
Brain Tissue Collection and c-Fos Staining • Protocol step
“repeated social defeat in mice increased c-Fos staining in brain regions associated with fear and threat appraisal”
Direct vendor pages are linked from the protocol above. This section stays focused on the full comparison view and the prep checklist.
Gather these items before starting the experiment. Check off items as you prepare.
Not explicitly stated in provided text • Not mentioned • Not mentioned • Not mentioned
Not explicitly stated in provided text • Not applicable • Not mentioned • Not mentioned
Not explicitly stated in provided text • Not applicable • Not mentioned • Not mentioned
Not mentioned • Not mentioned
Use this section as the page quality checkpoint. It keeps section navigation, evidence access, readiness, and verification meaning in one place.
Current status surfaces were computed from experiment data updated Feb 28, 2026.
Source access
Jump back into the original paper or the methods evidence section when you need exact wording, exclusions, or method-specific caveats.
This protocol has structured steps plus evidence quotes, and is ready for canonical sync.
Steps
9
Evidence Quotes
9
Protocol Items
3
Linked Products
0
Canonical Sync
Pending
What this means
The completeness score reflects how much structured protocol data is present: steps, methods evidence, listed materials, linked products, and paper provenance.
Computed from the current experiment record updated Feb 28, 2026.
Canonical Sync shows whether a ConductGraph-backed protocol is available for this experiment route right now. It is a sync-status signal, not a claim that every downstream vendor link or step detail is perfect.
Steps
9
Evidence
9
Specific Products
0/0
Canonical Sync
Pending
What this score means
The verification score reflects evidence coverage, subject detail, paper provenance, step depth, and whether linked products resolve to specific item pages instead of generic searches.
Computed from the current experiment record updated Feb 28, 2026.
A page can have structured steps and still need review when evidence is thin, product links are generic, or canonical protocol coverage is still pending.
What still needs work