Table 4.

Overview of behavioral assays of depression- and anxiety-like behavior, outlining the method as well as the common interpretation of results and behavioral profile associated with susceptibility

Paradigm	Duration	Description	Outcomes	Advantage	Disadvantage
Chronic Social Defeat Stress	Chronic (10 days)	Experimental mice experience brief aggressive encounters (5–10 min) in the home cage of an aggressive mouse and are then housed in the same cage separated by a divider to maintain sensory exposure with the aggressor. This is repeated with a new aggressor daily.	Social avoidance, reduced center time in open field, immobility in FST/TST, reduced sucrose preference, circadian and metabolic changes	Standardized protocol produces both susceptible and resilient mice modeling phenotypic divergence in stress adaptation using an ethologically relevant social stress	Not readily adaptable to female mice
Chronic mild stress/chronic unpredictable mild stress/chronic variable stress	Chronic (6 days –12 weeks)	Mice are exposed to daily mild stressors for a variable period. Stressors vary considerably between protocols but can include: Cage tilt, footshock, tail suspension, restraint, wet cage, social isolation, perturbation of light/ dark cycle, cage changing, temperature perturbation, cage shaking, intruder, noise	Reduced sucrose preference, immobility in FST/TST, increased latency to eat in a novel environment, decreased grooming.	Identical manipulations can be employed in males and females	Lack of standardization & detailed reporting of some protocols obstructs efforts to reproduce across labs
Learned Helplessness (LH)	Sub-chronic (2–3 days)	Mice are exposed to one or more sessions of repeated inescapable electric shock and later are given the opportunity to escape further signaled shocks	Failures to escape from escapable, signaled shock	Reproducible protocol across labs can produce a phenotypic split between learned helpless and non-learned helpless animals	Relevance to females has been questioned
Forced Swim/Tail Suspension	Acute (5 min–1 h)	Mice are suspended from their tail (TST) or placed in an inescapable body of water (FST)	Immobility in FST/TST	Quick & easy to conduct	Questions of relevance of single stressor