CUMSStress-Based
Background: BALB/cJ or C57BL/6J
Anhedonia3–4 weeks
Behavioral Despair4–6 weeks
Social Deficit4–6 weeks
Test Window4–8 weeks of stress protocol
Gold standard model for anhedonia. Rodents are exposed to a rotating sequence of mild stressors (tilted cage, wet bedding, food/water deprivation, light cycle disruption, restraint) for 4–8 weeks. Produces progressive anhedonia (reduced sucrose preference), behavioral despair, coat deterioration, weight changes, and HPA axis dysregulation. Critically, the depressive phenotype responds to chronic (3–4 weeks) but not acute antidepressant treatment, providing strong predictive validity.
Ideal for: Anhedonia-focused studies; chronic antidepressant screening with high predictive validity; modeling the gradual onset of depressive episodes.
Willner P. (2005). Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology, 52(2), 90-110. PMID: 16037678
CUMS Behavioral Battery
Sucrose Preference Test
Gold standard for anhedonia. Two-bottle choice between sucrose solution (1–2%) and water over 12–24 hours. CUMS mice show progressively reduced sucrose preference from ~85% to ~60% over 4 weeks.
View Sucrose Preference Test→Forced Swim Test
Measures behavioral despair via immobility time in a cylinder of water. CUMS increases immobility, reversible by chronic antidepressant treatment. Standard 6-minute test, score last 4 minutes.
View Forced Swim Test→Tail Suspension Test
Dry-land alternative to FST. Mice suspended by the tail for 6 minutes; immobility reflects behavioral despair. CUMS increases immobility. Avoids swim-stress and hypothermia confounds of FST.
View Tail Suspension Test→Open Field Test
CUMS reduces total locomotor activity and center zone exploration. Center time reduction reflects anxiety-depression comorbidity. Essential for ruling out locomotor confounds in despair tests.
View Open Field Test→Elevated Plus Maze
Captures the anxiety component of depression. CUMS mice spend less time in open arms, reflecting increased anxiety-like behavior — a common comorbidity in clinical depression.
View Elevated Plus Maze→CSDSStress-Based
Background: C57BL/6J (intruder) vs CD-1 (aggressor)
Anhedonia10 days
Behavioral Despair10 days
Social Deficit10 days
Test WindowDay 11+ (after 10-day defeat protocol)
C57BL/6J mice are subjected to 10 daily sessions of social defeat by a larger, aggressive CD-1 resident mouse (5–10 minutes physical interaction, then 24-hour sensory contact through a perforated divider). Uniquely separates mice into susceptible (~65%) and resilient (~35%) subpopulations based on social interaction ratio. Susceptible mice show social avoidance, anhedonia, and metabolic changes; resilient mice do not, despite identical stress exposure.
Ideal for: Studying resilience vs susceptibility mechanisms; social withdrawal as a depression endophenotype; epigenetic and transcriptomic studies of stress response.
Golden SA, et al. (2011). A standardized protocol for repeated social defeat stress in mice. Nat Protoc, 6(8), 1183-1191. PMID: 21799487
CSDS Behavioral Battery
Social Interaction Test
The defining assay for CSDS. Measures time spent near a social target (novel CD-1 mouse) vs empty enclosure. Social interaction ratio < 1.0 defines susceptibility; > 1.0 defines resilience.
View Social Interaction Test→Sucrose Preference Test
Susceptible mice show reduced sucrose preference (anhedonia) that correlates with social avoidance. Resilient mice maintain normal preference despite stress exposure.
View Sucrose Preference Test→Forced Swim Test
Increased immobility in susceptible mice reflects behavioral despair. Resilient mice show normal immobility levels. Useful for validating the susceptible/resilient classification.
View Forced Swim Test→Light-Dark Box
Susceptible mice spend more time in the dark compartment, reflecting anxiety-like behavior. Complements elevated plus maze for characterizing the anxiety-depression overlap.
View Light-Dark Box→Open Field Test
Reduced center time and total distance in susceptible mice. Distinguishes locomotor effects from anxiety-like behavior. Critical control for interpreting social interaction results.
View Open Field Test→Learned HelplessnessStress-Based
Background: C57BL/6J or CD-1
Anhedonia24 hours
Behavioral Despair24 hours
Social DeficitVariable
Test Window24–48 hours post-induction
Rodents exposed to inescapable foot shock (e.g., 60 shocks, 0.3 mA, 15 s duration, random intervals over 1 hour) subsequently fail to escape controllable shock in a shuttle box, despite having the ability to do so. The hallmark "helpless" phenotype — failure to escape — reflects a cognitive dimension of depression: the learned expectation that actions are futile. Not all animals become helpless (~50–70% susceptibility), enabling susceptibility studies.
Ideal for: Cognitive aspects of depression; rapid-onset models for acute drug screening; studying the neurobiology of helplessness and controllability.
Maier SF, Seligman ME. (2016). Learned helplessness at fifty: Insights from neuroscience. Psychol Rev, 123(4), 349-367. PMID: 27337390
Learned Helplessness Behavioral Battery
Passive Avoidance Shuttle Box
The defining test for learned helplessness. Measures escape latency and escape failures in a two-compartment shuttle box with escapable shock. Helpless mice show increased failures to escape.
View Passive Avoidance Shuttle Box→Forced Swim Test
Helpless mice show increased immobility, reflecting generalized behavioral despair beyond the shock context. Validates that helplessness extends to non-shock stressors.
View Forced Swim Test→Tail Suspension Test
Increased immobility in helpless mice. Provides a complementary despair readout without the swim-stress confound. Correlates with escape failure rate in the shuttle box.
View Tail Suspension Test→Sucrose Preference Test
Helpless animals show reduced sucrose preference, indicating anhedonia. Confirms that learned helplessness produces a broader depressive phenotype beyond escape deficits.
View Sucrose Preference Test→Open Field Test
Controls for locomotor effects of shock exposure. Reduced exploration and increased thigmotaxis in helpless mice reflect anxiety-like behavior.
View Open Field Test→Chronic CorticosteronePharmacological
Background: C57BL/6J
Anhedonia4–5 weeks
Behavioral Despair4–5 weeks
Social DeficitMild
Test Window4–7 weeks of treatment
Corticosterone (35 µg/mL) dissolved in drinking water, delivered ad libitum for 4–7 weeks. Produces chronic HPA axis activation mimicking the hypercortisolemia observed in ~50% of MDD patients. Non-invasive, no surgery or social manipulation required. Produces coat deterioration, reduced grooming, anhedonia, increased immobility in despair tests, and hippocampal neurogenesis suppression. Reversed by chronic fluoxetine treatment.
Ideal for: HPA axis-focused depression studies; neurogenesis-dependent antidepressant mechanisms; non-invasive chronic model without social or physical stressors.
David DJ, et al. (2009). Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron, 62(4), 479-493. PMID: 19477151
Chronic Corticosterone Behavioral Battery
Sucrose Preference Test
Progressive anhedonia develops over 4–5 weeks of corticosterone treatment. Two-bottle choice test shows reduced preference from ~85% to ~65%. Reversed by 3–4 weeks of chronic fluoxetine.
View Sucrose Preference Test→Forced Swim Test
Increased immobility after 4+ weeks of corticosterone. Responds to chronic but not acute antidepressant treatment, providing strong predictive validity.
View Forced Swim Test→Tail Suspension Test
Complementary despair test showing increased immobility. Corticosterone-treated mice show a clear response to chronic SSRI treatment in this assay.
View Tail Suspension Test→Elevated Plus Maze
Chronic corticosterone produces anxiety-like behavior (reduced open arm time) in addition to depressive phenotypes. Captures the anxiety-depression comorbidity.
View Elevated Plus Maze→Grooming Analysis
Automated tracking of grooming bouts, duration, and patterns. Chronic corticosterone reduces grooming and causes coat deterioration — a physical marker of depressive-like state.
View Grooming Analysis Module→
