Summary of stress models used to create anxiety models in rodents
| Stress model | Description | Source |
|---|---|---|
| CMS; CUS; CVS | Originally developed by Paul Willner as a model for depression, involves the subjugation of animals to a series of multiple, unpredictable stressors over a prolonged period; May vary in the combination and duration of stressors; Many limitations, such as difficulty to replicate | Willner, 1997; Lezak et al., 2017 |
| CSDS | Initially developed to model depression by Avgustinovich et al. (2005); was popularly adapted to investigate anxiety phenotypes by Krishnan et al. (2007); Study animal is introduced to the cage of a larger, aggressive animal (often a different strain of rat or mouse); Study animal is consider the “intruder”; aggressor animal is considered a “resident”; Exposure lasts for 10 min for 10 d, but may differ based on the researcher’s goals; Some animals may overcome CSDS-induced anxiety and are considered models for studying anxiety resilience; Limitations: sex-related differences (females tend not to participate in territorial related aggression); and injury to the model animal by the aggressor animal | Avgustinovich et al., 2005; Krishnan et al., 2007; Lezak et al., 2017 |
| Prenatal stress | Originally used in rats by William Thompson, this stress model involves the application of a stressor to a pregnant dam; later adapted to study anxiety-like behaviors in offspring by other researchers (Vallée et al., 1997); Considered a developmental form of stress; Stressors include, e.g., footshock, restraint stress, subjection to EDCs; for more comprehensive reading on variations used in this model, please refer to Weinstock (2017) | Thompson et al., 1962; Vallée et al., 1997; Lezak et al., 2017 |
| Postnatal stress | Administration of a stressor following the birth of pups and was first reportedly used by Krzysztof Janus (1987); Considered a developmental form of early life stress; The most commonly employed stressor is maternal separation in rodents, the time of separation is crucial for inducing anxiety-like phenotypes: separation at P3 to P4 tends to induce anxiety-like behaviors, while separation at P11 to P12 has been shown to cause the opposite effect of hyporesponsiveness | Murthy and Gould, 2018; Lezak et al., 2017; van Oers et al., 1998 |
CUS, Chronic unpredictable stress; CVS, chronic variable stress; P, postnatal day.