3. Stress by type of stressor

Author: Ulrich Brennecke
Review (2024): Dipl.-Psych. Waldemar Zdero

The type of stressor influences the location of the neurophysiological changes in the brain.

Stress causes changes in the dopaminergic system. Different stressors lead to different changes in the dopaminergic system. The effects of different types of stress on the brain and the dopaminergic system in particular can be found at Dopamine and stress In the section Dopamine in the chapter Neurological aspects.

The different types of stress are called stress protocols in the laboratory application for researching stress in rodents. These include chronic immobilization stress, chronic social stress and chronic (unpredictable) mild stress.

• 3.1. Stress protocols
  • 3.1.1. Chronic restraint stress (CRS)
  • 3.1.2. Forced swimming
  • 3.1.3. Cold stress
  • 3.1.3. Isolation stress
  • 3.1.4. Handling
  • 3.1.5. Noise stress
  • 3.1.6. Chronic social defeat stress (CSDS)
  • 3.1.7. Chronic (unpredictable) mild stress (CUMS, CMS)
• 3.2. Homotypic vs. heterotypic stress
• 3.3. Stress contagion / social transmission of stress
• 3.4. Types of stress and ADHD subtypes
• 3.5. Measurement protocols
  • 3.5.1. Tail suspension test (TST)

3.1. Stress protocols¶

Most studies on stress examine stress in rodents under laboratory conditions. Different types of stress are caused by different treatments.
As the stress protocols are not standardized, the following examples only show possible forms of application.

3.1.1. Chronic restraint stress (CRS)¶

According to the protocol for chronic immobilization stress, the animals are kept in a (ventilated and transparent) restraining device for 2 to 6 hours per day for 10 to 28 days. Chronic immobilization stress triggers rodent depression symptoms, which are measured by behavioral tests such as the sucrose preference test, the forced swim test and the tail suspension test.¹

Mice are placed in ventilated Plexiglas fixation devices (11.5 cm (length) × 3 cm (diameter) with air holes of 8-0.5 cm diameter) for 2 hours.²

Mice are wrapped in flexible wire mesh to prevent pressure points on the body and overheating.³

3.1.2. Forced swimming¶

Mice must swim for 2 minutes in tap water (10 cm deep) at room temperature (22 °C) in an open, cylindrical Plexiglas container [30.5 cm (height) × 30.5 cm (diameter)]. The water is changed between each animal.²
Mice have to swim for 10 minutes in water that is 40 cm deep and 23 degrees Celsius.³
Some studies use forced swimming in cold water⁴ or forced swimming in narrow cylinders⁵.

3.1.3. Cold stress¶

Mice are separated into individual polycarbonate cages and placed in a ventilated cooling chamber (4 °C) for 2 hours. The cages are cleaned daily and the empty cages are left in the cooling chamber overnight.²
Rats were brought into the cooling chamber in their home cages between 8 and 9 a.m. and kept at +4 °C for 3 hours.⁶

3.1.3. Isolation stress¶

Short-term isolation: 3 to 4-month-old mice were placed in individual polycarbonate cages for 2 hours while remaining in the animal housing room.²
Chronic isolation: Isolated housing of rats from the age of 3 months in Plexiglas cages⁷

3.1.4. Handling¶

The mice were lifted briefly and allowed to move freely on the hand (approx. 30 seconds).²

3.1.5. Noise stress¶

White noise, 1 hour at 100 dB with graduated fade-in and fade-out over a period of 2 to 3 minutes to avoid startle reactions.³

3.1.6. Chronic social defeat stress (CSDS)¶

The protocol for chronic social stress involves placing a single male (the intruder on which CSDS is tested) in the home cage of a larger male (aggressor, resident) for 5 to 10 minutes. There, the intruder is defeated by the resident animal. After this immediate physical interaction, the resident and intruder are kept in sensory contact for 24 hours. For 10 consecutive days, the intruders are exposed to the home cage of a new resident. After this CSDS exposure, the time of social interaction is measured.¹
There are two phenotypes:

• susceptible mice that develop depressive behaviors that manifest in reduced social interaction
• resistant mice that do not develop depressive behaviors

3.1.7. Chronic (unpredictable) mild stress (CUMS, CMS)¶

The protocol for chronic (unpredictable) mild stress involves exposing rodents to a series of (only comparatively) mild unpredictable stressors over 2 to 12 weeks in random order of priority, such as:⁸

• Night lighting
• Tilting the cage
• moist litter
• unpleasant noises
• Cage change
• Food/water withdrawal
• etc.

This stress protocol triggers persistent depressive behaviors and appears to mimic the stress-induced depression observed in depressed patients.
In another study on adolescent rats, it triggered ADHD and anxiety symptoms in adulthood.⁹

3.2. Homotypic vs. heterotypic stress¶

Heterotypical stress is made up of several stress experiences of different types of stressors. Homotypic stress, on the other hand, consists of repeated stress experiences of one type of stressor.
A sequence of different stress experiences causes different adaptation reactions in heterotypic stress and homotypic stress.
In the case of homotypic stress, a healthy adaptation reaction occurs far more frequently, in which the stress system reacts to the repetitive stressors with increasingly weaker stress reactions. In the case of heterotypic stress, on the other hand, the stress response often fails to adapt. This remains equally pronounced even with repeated stress experiences (maladaptation).¹⁰

3.3. Stress contagion / social transmission of stress¶

Stress can arise / be transferred simply by observing another person’s experience of stress.¹¹¹²
Children showed symptoms of stress when they perceived acute stress in a parent.¹³¹⁴
The stronger the identification between people, the more they feel that they belong to a common group, the more stress experienced by an individual also leads to an increase in cortisol levels in others in the group who experience it.¹⁵¹⁶ A position of power could increase stress contagion, possibly due to an associated sense of responsibility.¹⁷ If the observer had previously experienced the stressful experience themselves, the transmission of the stress sensation during the observation was lower.¹⁷
Another study also found a social transmission / contagion of stress, but not a dependence on the sense of identification.¹⁸
Empathic stress, i.e. socially transmitted stress, does not appear to correlate with mimicry of facial features.¹⁹

Stress transmission is also found in animals.²⁰
Pain can also be transmitted socially, even between animals.²¹ This mechanism is related to the social transmissibility of the placebo effect.²²

3.4. Types of stress and ADHD subtypes¶

Different stressors correlated with different ADHD subtypes:

Neglect of supervisory duties that put the child at risk of physical or psychological harm correlated with ADHD-I (inattentive type, OR 1.6) as well as with ADHD-HI/ADHD-C (hyperactive type, OR 1.5).
In contrast, physical neglect only correlated significantly with ADHD-I (OR 2.1), but not with hyperactivity.²³
ADHD-I correlated with:

• sexual physical abuse (OR 2.6, + 160 %)
• physical neglect (OR 2.1, + 110 %)
• physical abuse (OR 1.6, + 60 %)
• Neglect of supervisory duties (OR 1.6, + 60 %)
  ADHD-HI/ADHD-C correlated with:
• Neglect (OR 1.5, + 50 %)
• physical abuse (OR 1.3, + 30 %)
• not significantly against it:
  • physical neglect
  • sexual contact abuse

3.5. Measurement protocols¶

3.5.1. Tail suspension test (TST)¶

The tail of the mouse is attached to a smooth Plexiglas plate and the mouse is hung on the roof of a sound-absorbing box. The movements of the animals are recorded for several minutes with a camera.²⁴