Table 1

Summary of stress models used to create anxiety models in rodents

CMS; CUS; CVSOriginally 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
CSDSInitially 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 stressOriginally 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 stressAdministration 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.