Maladaptive behaviors are abnormal behaviors that manifest as a result of environmental triggers such as stress or even seasonality.
Maladaptive behaviors are a type of abnormal behavior which can occur in mice that are otherwise normal and healthy. Maladaptive behaviors happen largely due to the environment. When mice are placed in an environment that is not natural for them, they are likely to react and develop maladaptive behaviors.
An abnormal environment may elicit abnormal behaviors. This is obvious in some instances of infanticide. Infanticide is likely to be observed under extrenuating environmental conditions, such as extreme cold temperatures. Essentially, an environmental stimulus triggers an abnormal behavior. Therefore, abnormalities that occur due to the environment are typically classified as maladaptive behaviors.
Maladaptive behaviors stand in contrast to malfunctional behaviors . Malfunctional behaviors are abnormal behaviors occurring in mice that are themselves abnormal. They have genetic mutations and are physiologically malwired.
Maladaptive behaviors are composed of several other behaviors. The following behaviors drive and enable specific maladaptive behaviors to happen:
- Nose-poking: Nose-poking refers to the behavior of using the nose to press something, typically a food dispenser’s lever in laboratory conditions. This behavior is crucial to many tests and tasks which use the operant chamber. When performed in excess or at inappropriate moments, nose-poking is associated with impulsivity.
- Biting: Biting is a behavior that involves using the teeth to contact piercingly an object or the skin such that it leads to a break, nick, or scratch. Biting can be observed in a variety of contexts, including social biting, predatory biting, and food biting. Impulsive aggression and impulsive eating are comprised of high instances of biting.
- Scratching: A mouse uses its hind-limbs to vigorously or quickly scratch its back, head, or neck. Scratching bouts are usually short-lived, resolve quickly, and do not last long. When a mouse is scratching itself repeatedly and continuously, it can be considered as an abnormal behavior because it ends up causing skin lesions.
- Jumping: A mouse will use its limbs to push off the ground and suspend itself momentarily in the air. High levels of repetitive jumping is a commonly observed stereotypy in mice.
- Chewing: Chewing is the repeated biting motion done in the context of feeding behaviors. As a stereotypy, chewing is performed in excess and under inappropriate circumstances.
Types of Behaviors
The following behaviors can be classified as being maladaptive when they are triggered by environmental conditions:
- Infanticide: Infanticide is the act of killing one’s own newborn pup. In the laboratory, infanticide is a maladaptive, abnormal maternal behavior. The mother may perform infanticide shortly after giving birth.
- Impulsive behaviors: Impulsivity, also referred to as compulsive behaviors, is characterized by repeating flexible behaviors driven by an inappropriate goal.
- Stereotypies: Stereotypy is a general term that refers to any behavior that is performed in excessive repetition without a clear goal.
- Ulcerative dermatitis: Ulcerative dermatitis is a type of skin disorder that is associated with bacterial flora. The disorder occurs due to excessive scratching.
This collection of behaviors can also be classified as malfunction, but only if the underlying cause is genetic, not environmental.
Function of Maladaptive Behaviors
None. Maladaptive behaviors are considered to be abnormal and usually poor, sometimes harmful, behavioral responses to environmental factors.
Application of Maladaptive Behaviors
Maladaptive behaviors are triggered responses which occur due to the environment. Thus, they are likely to be observed under the following environmental circumstances:
- Stressful environmental conditions: Stressful environmental factors have been shown to lead to maladaptive behaviors like impulsivity.
- Social isolation: Since mice are social creatures, stressful situations like isolation lead to behavioral abnormalities including, but not limited to, impulsivity, aggression, and anxiety.
- Overcrowded housing: Overcrowding occurs when mice are living in tight and restrained conditions. Malfunctional behaviors like infanticide have been observed to occur as a result of overcrowding.
- Seasonality: Seasonality is another environmental effect that can influence behaviors. For example, ulcerative dermatitis has the highest peak incidence occurring around midsummer.
- Humidity: Humidity is yet another environmental factor that plays a role in the development of ulcerative dermatitis. In fact, a large majority of cases will occur in an environment with 35 to 45% humidity levels.
- Age: Adolescent mice aged postnatal day 36-59, are known to be more impulsive than older mice. Thus, age is a factor that affects the frequency of impulsive behaviors displayed.
- Overly cold temperatures: Cold temperatures trigger can also trigger maladaptive behavior like infanticide. It is hypothesized that this may occur due to environmental influence altering hypothalamic homeostasis.
Is the Behavior Malfunctional or Maladaptive?
Malfunctional behaviors stand in contrast to maladaptive behaviors. Maladaptive behaviors are largely due to environmental causes or triggers. When mice are placed in an environment that is not natural for them, they are likely to react and develop maladaptive behaviors.
The following research techniques have been used to study maladaptive behaviors:
- Behavioral studies: Behavioral studies are very useful for establishing how maladaptive behaviors look like in action. Behavioral studies enable the researcher to quantitatively assess maladaptive behaviors across mouse strains and environments.
- Pharmaceutical studies: Pharmaceutical studies are used when studying the effect of certain drugs or supplements on maladaptive behaviors. This is done in order to determine to what extent a drug can affect the maladaptive behavior of interest.
- Genetic studies: Genetic studies are useful for identifying potential genes involved in the etiology of maladaptive behaviors in which the combined forces of environment and genes affect the outcome. Via genetic studies, a clearer understanding can be acquired regarding the reasons that maladaptive behaviors interact on an environmental level in mice with a susceptible gene profile. Thus, genetic studies are important in order to establish the intertwined relationship that genes and the environment have over the development of maladaptive behaviors.
Behavioral Tests for Assessing Maladaptive Behaviors
Since maladaptive behaviors are comprised by various behaviors, there are several different behavioral tests that can be used to study them, including:
- Parental behavior test: In the parental behavior test, mice are tested for their parental behavior instincts. This test is of interest to researchers assessing infantice. One day before the test, a mouse is provided with extra material (such as cotton), in order to make its nest, a behavior that naturally comes to them. Then, the next day, a newborn pup is placed in the corner of the cage that is far away from the nest. The experimental mouse is measured by its reaction, whether it retrieves the pups, ignores it, or attacks (and kills) it. Typically, foster pups are used for this test. However, it is also possible to use pups which are genetically related to the test subject.
- The stop-signal task (SST): The SST is a type of operant test where a mouse is expected to react a certain way, usually trained to do so using an Operant Chamber. This task is used to assess impulsivity/compulsive behaviors. During the SST, a go signal is used to initiate a motor response. On certain trials, mice will suddenly see the stop signals and researchers measure the time it takes for mice to stop, i.e. inhibit a motor response. The longer that it takes for a mouse to initiate a stop response, the more impulsive they are and the poorer the inhibitory control they possess.
- The Go/No-Go task: The Go/No-Go task is another assessment used for measuring compulsive behavior. It is also sometimes referred to as discriminatory training. Essentially, this task assesses executive function by measuring how well a mouse can respond (the Go condition) in order to receive food or withhold a response (the No-Go condition). From the Go/No-Go, behavioral measurements acquired include: hits (the number of responses performed correctly), false alarms (responses which occur during the No-Go interval), and latency to respond on the Go and No-Go conditions.
- Resident-intruder test: To test if a mouse is impulsively aggressive, the Resident-Intruder test can be employed. Using a sociability chamber, a non-aggressive intruder is placed in the cage. If the resident mouse is highly aggressive without any provocation, they are considered to be impulsively aggressive.
Behavioral Assessment Techniques
To supplement the tests mentioned above, the following behavioral assessment techniques are frequently used in research settings:
- Video recording: Since maladaptive behaviors like infanticide can occur at any point during the day, constant video surveillance is necessary, in order to capture the moment. Otherwise, researchers run the risk of not observing or even misclassifying the behavior. For example, passive cannibalism is often mistaken for infanticide which is a completely different behavior with different motivations. Therefore, video recording is absolutely necessary, in order to record behaviors that occur outside the researcher’s window of observation.
- Rating scales: Maladaptive behaviors can also be measured by using rating scales. For example, ulcerative dermatitis and stereotypy can both be measured using their own respective rating scales. Rating scales quantify the extent and level that maladaptive behavior is displayed during a pre-set observational period.
- Infrared beams: The use of behavioral monitoring systems, such as the SmartCage System, is becoming more and more popular in behavioral neuroscience. Infrared beams automatically detect and quantify behaviors. This technique is especially common for measuring stereotypy as this class of behaviors occur rapidly.
The following findings have been established, showing the effects drugs and medicine have on maladaptive behaviors:
Oxytocin Reduces Infanticide
About 60 to 90% of female house mice will kill unrelated newborns. Oxytocin is a hormone known for its involvement in shaping positive social attachments. Oxytocin, administered subcutaneously via intracerebroventricular injections, can significantly lower infanticidal behavior, possibly by acting directly on the central nervous system.
Vitamin E Improves Ulcerative Dermatitis Severity
A study by Lawson et al. showed that adding 3000 IU of vitamin E to mice’s ad libitum diet for 8 weeks is associated with positive treatment results of ulcerative dermatitis. In this study, 45% of mice with ulcerative dermatitis with vitamin E in their diet had complete lesion recovery and hair regrowth. It took about 2 to 5 weeks for mice to completely repair from their lesions.
Fluoxetine Can Reduce Aggressive Impulsivity
Social isolation, as mentioned previously, has been linked with several diverse behavioral outcomes including impulsivity. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is commonly used to treat depression. It is also used in personality-disordered subjects in order to treat impulsive aggressive behavior. When socially isolated mice are treated with fluoxetine, aggressive impulsivity is subsequently reduced.
Diesel Exhaust Particulate Matter Leads to Impulsivity in Offspring
An example of how environmental factors can influence behavior is exposure to air pollution. Air pollution is a serious problem that affects much of the urban population. To model air pollution exposure in mice, diesel exhaust is used because it is the largest contributor of particulate matter that is airborne. Thus, chemical exposure to diesel exhaust is a key model for capturing the environmental ambient particulate matter exposure associated with living in urban metropolitan areas.
To assess how particulate matter exposure affects newborn pups, pregnant dams can be exposed to diesel exhaust at various concentrations. Then, when their offspring reach a suitable age, they can be subjected to a range of cognitive tests, such as the cliff avoidance test which is a measure of impulsive behavior.
Offspring that are maternally exposed to diesel exhaust particulate matter are more impulsive than non-exposed controls. The exposed offspring display a much lower latency to fall off the visual cliff avoidance test, indicating that they have higher levels of impulsivity. This suggests that environmental factors like air pollution can ultimately influence the cognitive functioning of newborns.
Mouse Strains Exhibiting Maladaptive Behaviors
Theoretically, any strain can show maladaptive behaviors. Maladaptive behaviors refer to any abnormal behaviors which occur beyond the particular mouse strain’s baseline profile of behaviors. For example, if a hyperactive mouse becomes hypoactive due to environmental factors, the change may be a maladaptive behavior. In this section, we will take a look mostly at how C57BL/6J mice demonstrate maladaptive behaviors.
C57BL/6J Mice Exhibit High Levels of Infanticide
Both male and female C57BL/6J mice are highly prone to killing unknown young pups.
The degree with which male C57BL/6J mice perform infanticide varies with age. When they are as young as 35 days old, male C57BL/6J mice are already showing signs of aggression towards newborns. Castration significantly lowers C57BL/6J males’ tendency for infanticide.
Female C57BL/6J mice are also aggressive towards newborns, averaging roughly a 60% chance of exhibiting infanticide.
DBA/2 (DBA) mice have been found to show environmentally-induced stereotypy when subjected to food restriction for 9 straight days. To be more specific, abnormally high levels of climbing can be observed in DBA mice as their response to receiving no food. This behavioral stereotypy is also observable in C57BL/6 mice when subjected to food-restriction, but the subsequent stereotypy is more severe in DBA mice which suggests a genetic component interacting with an environmental factor.
Maladaptive Behaviors in Disease Models
Maladaptive behaviors can be observed in many disease models, including the following:
Addiction Models and Impulsive Behaviors
Addiction in mice can be modeled environmentally (but it can also be modeled genetically). Environmentally, mice are given extended access to alcohol (for about 70 days) within their cage. Then, alcohol preference and addiction-like behaviors are measured based on how much and how frequently they drink it.
Environmentally-Induced Stereotypy Models
Stereotypy can be environmentally-induced (but also genetically, as well). If a stereotypical behavior manifests as a response to an environmental factor, then it is classified as an environmentally-induced stereotypy. Thus, behavioral researchers can manipulate the environment in a controlled fashion in order to study how mice can develop stereotypy.
The following experimental approaches can bring about environmentally-induced stereotypies:
- Housing in restrictive cages: Mice that are housed in barren and restrictive cages are extremely likely to display excessively repetitive/stereotypic behaviors.
- Food restriction: Certain mouse strains show adverse behavioral effects such as developing specific stereotypies as a result of food restriction, as is the case with DBA mice mentioned previously.
High-fat Induced Obesity and Ulcerative Dermatitis
Mice can become obese through an environmental intervention of a high-fat diet. This also translates to human cases of obesity, since a large proportion of cases is caused by having a high-fat diet for an extended period of time. Some mice that are given a high-fat diet will not only become obese, but will also show behavioral ulcerative dermatitis.
Do Maladaptive Behaviors Affect Behavioral Assessment?
Maladaptive behaviors definitely affect behavioral assessment. In this section, we will cover how these behaviors are treated in behavioral research.
In behavioral research, it is important to establish that mice are not demonstrating impulsivity/compulsive behaviors. Impulsivity affects behavioral assessment because it is a complex psychological construct that can influence a mouse’s behavioral predisposition.
Thus, at a minimum, when examining for impulsivity, initial behavioral screens include motoric tests of function and activity. Any other spontaneous behaviors can be examined in further detail by using the Elevated Plus-Maze, Open Field, or the Novel Object Test.
Mice that demonstrate stereotypical behavior are also an issue for behavioral assessments. Their overactive behavior can significantly influence behavioral observations. Thus, if stereotypy is not the behavior of interest, stereotypical mice are typically removed from research experiments. To date, there is no steadfast way to improve stereotypy in experimental mice.
As mentioned previously, ulcerative dermatitis is a serious condition that affects mice. Thus, it is a serious problem for behavioral researchers, as well. If an experimental mouse develops ulcerative dermatitis, it is removed from the study until its condition improves. Since ulcerative dermatitis is fairly common amongst experimental mice, researchers are working to develop and establish simple interventions that can prevent or even quickly improve this condition. Currently, toenail clipping is the most simple and effective intervention that exists.
- Maladaptive behaviors are behaviors which do not aid the mouse in adapting to its environment, thus are maladaptive in nature.
- Maladaptive behaviors are a type of abnormal behavior that can occur in mice that are otherwise normal and healthy.
- When mice are placed in an environment that is not natural for them, they are likely to react and develop maladaptive behaviors.
- The following behaviors drive and enable specific maladaptive behaviors to happen: nose-poking, biting, scratching, jumping, and chewing.
- The following behaviors can be classified as being maladaptive when they are triggered by environmental conditions: infanticide, impulsive behaviors, stereotypies, and ulcerative dermatitis.
- Maladaptive behaviors are considered to be abnormal and usually poor, sometimes harmful, behavioral responses to environmental factors.
- The following environmental circumstances may trigger the development of maladaptive behaviors: stressful environmental conditions, social isolation, overcrowded housing, seasonality, humidity, age, and overly cold temperatures.
- Maladaptive behaviors can be studied using research techniques such as behavioral studies, pharmaceutical studies, and genetic studies.
- Behavioral tests that are used to study maladaptive behaviors vary according to the specific behavior of interest, but the list includes parental behavior test, video recording, rating scales, infrared beams, the stop-signal task, and the go/no-go task.
- Pharmaceutical studies have shown that drugs and medicine can affect maladaptive behaviors, for example:
- oxytocin reduces infanticide,
- vitamin E improves ulcerative dermatitis severity.
- Maladaptive behaviors manifest differently across mouse strains. For C57BL/6J which are standard control mice, the following observations have been made: C57BL/6J mice exhibit high infanticide levels. Low instances of maladaptive behaviors are also seen in C57BL/6J mice for stereotypy and impulsivity.
- Maladaptive behaviors are also captured by disease models.
- For example, addiction models that involve impulsive behaviors can be seen in mice that have long-term access to alcohol.
- Stereotypy models can be induced via environmental conditions such as food restriction and restrictive housing.
- Access to a high-fat diet induces obesity and is associated with the development of ulcerative dermatitis.
- All maladaptive behaviors affect behavioral assessment in one way or another. Thus, behavioral researchers are trying to find ways to control for and limit instances of unwanted maladaptive behaviors.
- Weber, Elin M., et al. “Pup mortality in laboratory mice- nfanticide or not?.” Acta Veterinaria Scandinavica 55.1 (2013): 83.
- Heiming, Rebecca S., et al. “Living in a dangerous world decreases maternal care: a study in serotonin transporter knockout mice.” Hormones and behavior 60.4 (2011): 397-407.
- Koike, Hiroyuki, et al. “Behavioral abnormality and pharmacologic response in social isolation-reared mice.” Behavioural brain research 202.1 (2009): 114-121.
- Neuhaus, Brit, et al. “Experimental analysis of risk factors for ulcerative dermatitis in mice.” Experimental dermatology 21.9 (2012): 712-713.
- Powell, Susan B., et al. “A rodent model of spontaneous stereotypy: initial characterization of developmental, environmental, and neurobiological factors.” Physiology & behavior 66.2 (1999): 355-363.
- Kastenmayer, Robin J., Michele A. Fain, and Kathy A. Perdue. “A retrospective study of idiopathic ulcerative dermatitis in mice with a C57BL/6 background.” Journal of the American Association for Laboratory Animal Science 45.6 (2006): 8-12.
- Dent, Claire L., and Anthony R. Isles. “An Overview of Measuring Impulsive Behavior in Mice.” Current protocols in mouse biology 4.2 (2014): 35-45.
- Sasamori, Hitomi, et al. “Assessment of impulsivity in adolescent mice: A new training procedure for a 3-choice serial reaction time task.” Behavioural brain research 343 (2018): 61-70.
- McCarthy, Margaret M. “Oxytocin inhibits infanticide in female house mice (Mus domesticus).” Hormones and Behavior 24.3 (1990): 365-375.
- Gubner, Noah R., et al. “Strain differences in behavioral inhibition in a Go/No-go task demonstrated using 15 inbred mouse strains.” Alcoholism: Clinical and Experimental Research 34.8 (2010): 1353-1362.
- Lawson, Gregory W., et al. “Vitamin E as a treatment for ulcerative dermatitis in C57BL/6 mice and strains with a C57BL/6 background.” Journal of the American Association for Laboratory Animal Science 44.3 (2005): 18-21.
- Yokota, Satoshi, et al. “Exposure to diesel exhaust during fetal period affects behavior and neurotransmitters in male offspring mice.” The Journal of toxicological sciences 38.1 (2013): 13-23.
- Cabib, Simona, and Nunzio Bonaventura. “Parallel strain-dependent susceptibility to environmentally-induced stereotypies and stress-induced behavioral sensitization in mice.” Physiology & behavior 61.4 (1997): 499-506.
- Radwanska, Kasia, and Leszek Kaczmarek. “Characterization of an alcohol addiction-prone phenotype in mice.” Addiction biology 17.3 (2012): 601-612.
- Adams, Sean C., et al. “A ‘pedi’ cures all: toenail trimming and the treatment of ulcerative dermatitis in mice.” PloS one 11.1 (2016): e0144871.
- Liu, Lumei, et al. “The effects of Dietary Fat and iron interaction on Brain regional iron contents and stereotypical Behaviors in Male c57Bl/6J Mice.” Frontiers in nutrition 3 (2016): 20.