Active BehaviorGeneral Activity BehaviorMouse Ethogram

Mouse Ethogram: Abnormal Behaviors

By November 20, 2019 No Comments

Definition

Abnormal behaviors are a collection of behaviors that are not considered to be normal for a mouse. There are several different types of abnormal behaviors which can be observed across a variety of situations and circumstances.

Overview

Abnormal behaviors are a type of active behavior. Depending on the abnormal behavior, it may be further classified as a grooming behavior or a maternal behavior, for example.

A behavior can be abnormal and affect a mouse and/or its cagemates on many different dimensions, including physiologically, socially, or psychologically. So, any behavior that can be destructive or seriously disturbing to a mouse’s well-being and/or its cagemates’ is considered to be an abnormal behavior.

Abnormalities can be observed due to two major factors: genetics and/or environment.

Malfunctional Behaviors: Abnormal behaviors due to genetics

Abnormalities that are observed with a genetic cause are most likely to be categorized as a malfunctional behavior. Mice that are abnormal genetically are likely to be abnormal behaviorally, as well. Such is predominantly the case with barbering where mice compulsively groom. There are many genetically abnormal mice that demonstrate higher levels of barbering behavior than normal wild-type mice.

Maladaptive Behaviors: Abnormal behaviors due to environment

Abnormalities that occur due to the environment are typically classified as maladaptive behaviors. On the other hand, an abnormal environment may elicit abnormal behaviors as well. This is obvious in some instances of infanticide. Infanticide is likely to be observed under extrenuating environmental conditions, such as extreme cold temperatures. Thus, an environmental stimulus triggers an abnormal behavior.

Behaviors Associated with Abnormal Behaviors

Abnormal behaviors are complex and are composed of other behaviors. Below is a brief overview of behaviors which make up abnormal behaviors:

  • Biting: In the case of abnormal or aggressive forms of grooming behaviors, a mouse may bite itself or another mouse and subsequently remove fur and/or whiskers. Excessive biting can be observed in the instance of barbering.
  • Scratching: A mouse will perform scratching motions using its forelimbs or hindlimbs in order to alleviate the feeling of itchiness. Ulcerative dermatitis is the abnormal behavior associated with excessive scratching levels.
  • 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.
  • Bar-mouthing: Bar-mouthing, also known as ‘bar-biting’ or ‘bar-gnawing’, is an abnormality that can occur as a form of stereotypy. A mouse will bite the bars of its home cage repetitively. Obviously, this is a stereotypy that can only be seen in captivity.
  • Circling: Circling refers to a mouse’s motion. The mouse is moving repetitively and following a circular path. Circling is typically classified as a stereotypy.
  • Route-tracing: Route-tracing is a less common form of stereotypy, but it still happens. When route-tracing, a mouse is essentially following or running over the same cage pattern three times or more.
  • 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.
  • Climbing: Climbing is also displayed as a stereotypy. A mouse climbs by using props in its environment to move vertically in space in an upwards direction.

Types of Abnormal Behaviors

The following behaviors are considered to be different kinds of abnormal behaviors which a mouse is susceptible to exhibit.

  • Barbering: Barbering is a grooming behavior wherein a mouse plucks or excessively grooms itself or another mouse. Depending on the context, barbering may be either an abnormal behavior or agonistic behavior. A mouse may barber itself or, in the case of cage-mate plucking or ‘social barbering,’ it may barber other mice.
  • Self-grooming: When self-grooming is performed in excess, it is considered to be an abnormality because, as a result, the mouse may suffer from self-inflicted wounds and lesions.
  • Infanticide: Whenever a pup is killed by its parent or an unrelated mouse, it is considered to be a case of infanticide or infanticidal behavior.
  • Impulsive/Compulsive Behaviors: Compulsive behaviors are goal-directed (unlike stereotypies) and involve more flexible/variable goal-directed behavior. These types of behaviors are classified under the term of Abnormal Repetitive Behaviors (ARBs), a category of abnormal behavior that is characterized by repetition.
  • Stereotypy: Rodent stereotypy is an abnormal behavior that broadly refers to any type of abnormal behavior that is repetitive in nature. Stereotypic behaviors are sometimes used in obsessive compulsive disorder models. In the research field, mouse stereotypies are considered to be good models for human stereotypies, especially for models of autism and schizophrenia. Stereotypy is another type of ARBs, but is performed without a goal or function.
  • Ulcerative dermatitis: Ulcerative dermatitis is a type of skin disorder that is associated with bacterial flora. The disorder occurs due to excessive (thus, abnormal) levels of scratching which causes a lesion. Eventually, ulcerative dermatitis manifests. It is a serious condition that occurs frequently in animal research using mice.
  • Depressive-like behaviors: Depressive-like behaviors are a collective bunch of behaviors which as a group are believed to be representative of depression as seen in humans. Depressive-like behaviors are characterized by immobility, interaction deficits, and exploration deficits.
  • Anxiety-like behaviors: Anxiety-like behaviors are a group of behaviors which collectively represent the phenotype of anxiety as it is observed in humans. Anxiety-like behaviors are assessed in mice using a battery of specialized mazes and apparatuses.

Function of Abnormal Behaviors

Since abnormal behaviors are considered to be outside the range of normal or acceptable behaviors for a mouse, their function is poorly understood. Some behaviors may not even have a functional role while others may, somehow, end up serving a beneficial, evolutionary purpose in certain situations, as is the case for infanticide.

  • To increase their own pups’ chance for survival: Recent research is making the argument that non-parental infanticide may be an adaptive behavior. Male (or female) mice which perform infanticide on other mice’s pups invariably increase their own chances for reproductive success. By killing others’ pups, there will be more resources available for their own pups, thus increasing the chance of survival.
  • To reduce overcrowding: Infanticide is also exhibited during stressful or overcrowded conditions. By killing their own pups, mothers are ensuring their own survival during tough times when resources are limited, in order to get a chance to reproduce at a later point in time.

Application of Abnormal Behaviors

Depending on the type of abnormal behavior, it may be observed under a variety of situations.

  • A mouse has genetic mutations or physiological issues: Many abnormal behaviors have some genetic ties. Although, environment also plays a role in the development of abnormal behaviors, genetic correlations and mutations have been linked to a multitude of abnormalities in mice.
  • Under environmental stress: Environment is another major factor influencing the development of abnormal behaviors in mice. Stressful living conditions are liking to illicit abnormal behaviors such as infanticide.
  • Under laboratory conditions: Being under superficial laboratory conditions is another factor that is likely to influence the development of abnormal behaviors. Certain abnormalities like ulcerative dermatitis are seen in high numbers in mice living in captivity.
  • In group housing: Higher rates of abnormal behaviors are seen in group housed mice when compared to mice living in individually housed cages.

Research Techniques

Since abnormal behaviors vary far and wide in their characteristics, there are many research techniques that can be used to study abnormal behaviors. In order to study abnormal behaviors, research techniques must be employed based on the experimental question or variable of interest. These techniques and methods are used for studying abnormal behaviors:

  • Behavioral studies: Behavioral studies are very useful for studying abnormal behaviors because they enable the researcher to profile, describe, and quantitatively assess abnormal behaviors across mouse strains and interventions.
  • Pharmaceutical studies: Pharmaceutical studies are used when studying the effect of certain drugs or supplements on abnormal behaviors. This is done in order to determine how a drug will affect the manifestation of an abnormal behavior’s phenotype. Since abnormal behaviors in mice typically model diseases seen in humans, pharmaceutical studies play a key role.
  • Genetic studies: Genetic studies are useful for identifying potential genes involved in the etiology of abnormal behaviors. Through genetic studies, a better understanding can be gained of the reasons that an abnormal behavior manifests.
  • Video recording: Video recording is used across most, if not all, behavioral studies, especially those studying abnormal behaviors. The reason for this is that videotapes can capture and record behavior, allowing the researcher to observe and count all instances of the behavior, ultimately reducing the frame of error. This is especially useful since some abnormal behaviors, such as stereotypy, can occur in rapid succession, making it difficult to quantify all expressed behaviors in real-time.

Behavioral Tests for Abnormal Behaviors

A variety of behavioral tests can be used in order to study the different types of abnormal behaviors.

  • The Open Field Test: In the Open Field Test, mice are placed in a cage that is closed at the sides (in order to prevent escape) but open from above. This test is used in order to investigate anxiety and exploratory behaviors. Some research studies utilizing the Open Field Test may take note of instances of self-grooming behaviors if they occur during the observational period.
  • Social Interaction Test: The Social Interaction Test is useful for observing grooming behaviors which happen in a social context. In this test, two mice are placed together in the same cage and their behavior is observed. Allogrooming and cagemate barbering, since they are types of grooming behaviors which occur in a social context, are likely to be observed within a social interaction between two mice.
  • Three-Chamber Test: The three-chamber test, sometimes referred to as the Sociability Chamber, is used to evaluate cognition expressed through general sociability using both familiar and novelty mice. A mouse will spend more time exploring a novelty mouse in the chamber than it will spend exploring a familiar one. This test helps in identifying deficits related to sociability in mice. Even though the three-chamber test is reserved for studying social interaction, grooming behaviors will naturally be expressed during the observation period and a researcher may choose to quantify them as a part of their analysis.
  • The Tube Dominance Test: Social or cagement barbering can be observed in an agonistic setting, such as the ones created in the Tube Dominance Test. In this test, two mice are placed in a tube from either end and can only move forwards.
  • The Resident-Intruder Test: In this test, when an unknown mouse is placed in the cage in which a single mouse resides, an agonistic encounter is extremely likely to occur. In this case, barbering may be performed by the more dominant mouse.
  • Parental Behavior test: In the parental behavior test, mice are tested for their parental behavior instincts. One day before the test, a mouse is provided with extra material (such as cotton), in order to make a nest. 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.
  • Infrared Beams: The use of behavioral monitoring systems, such as the SmartCage System, is becoming more and more popular in behavioral neuroscience. These systems can detect and quantify motion via infrared beams automatically (thus, eliminating the possibility of investigator bias that’s present when measuring recorded videos). When the infrared beams are interrupted (due to motion) the system detects those changes and quantifies the stereotypical motion. Thus, many variables can be automatically measured, including sleep/inactive states, wake/active states, various locomotion parameters (like travel time and travel distance), rearing counts, movement patterns (such as rotation or cycling), and regional distribution. Thus, a lot of data is automatically acquired in preparation for the behavioral analysis. Such automated systems are useful for studying phenotypes of abnormal mice, stereotypy, toxic compounds and their effect on abnormal behavior, as well as pharmaceutical and supplemental treatments for abnormal behavior. However, there are some general limitations to using automated systems, such as if the mouse’s behavior is breaking/interrupting the same beams, the behavior may be registered as a stereotypy when it is not (like grooming or nibbling).
  • Rating systems: Rating systems classify the extent of certain behaviors into predefined categories. This enables researchers to measure and quantify behaviors and compare them across groups and/or treatment conditions. For more on this topic, check out the following: Rating Systems in Stereotypy and Rating Systems in Ulcerative Dermatitis.

Pharmaceutical Studies on Abnormal Behaviors

Since abnormal behaviors are in general considered to be unwanted granted that they are not in line with a mouse’s normal behavioral profile, there are plenty of pharmaceutical studies done that try to minimize or eliminate these behaviors in mice. Many of the abnormal behaviors which exist in mice serve as a model of human diseases which gives further incentive for trying to reduce their abnormality through pharmaceutical since this may eventually lead to a breakthrough that would also substantially help humans too. This section is an overview of findings from pharmaceutical studies.

Barbering and Pharmaceutical Studies on Abnormal Behaviors

  • Clomipramine reduces barbering in trichotillomania mice: Clomipramine is a tricyclic antidepressant that is able to inhibit serotonin reuptake system. Mice which have a genetic mutation that knockouts the nitric oxide synthase (NOS2) gene are used as an animal model of trichotillomania due to their high levels of barbering behavior. However, when given clomipramine, these mice will barber significantly less after 10-20 days of treatment when compared with untreated NOS2 mice. More information will be given about NOS2 mice in the upcoming Mouse Strains section.
  • Estradiol injections reduce barbering in trichotillomania mice: Trichotillomania, defined as repetitive hair-plucking, is related to Obsessive-Compulsive Disorder and is a common disorder in women. Not much is known regarding the disorder’s mechanisms and biological causes. In mice, barbering is a hair-plucking behavior that has been validated as a model for trichotillomania. Correlations have been found between the onset of trichotillomania and changes in reproductive physiology, leading to the hypothesis that reproductive hormones may play a role in the disease. Estrogen doses are able to influence the brain’s catecholamines and endogenous opiates that are known to regulate and interact with corticostriatal loops, which are implicated in motor and planning behavior. 17β-estradiol benzoate injections reduce barbering in females when compared to females on a vehicle solution. The effect of estrogen injections implies that sex hormones are critical for determining the onset of trichotillomania.

Oxytocin Reduces Infanticide

It is estimated that roughly 60 to 90% of female house mice will kill unrelated pups.  Subcutaneous and intracerebroventricular injections of oxytocin are able to significantly lower infanticidal behavior, possibly by acting directly on the central nervous system.

Stereotypies and Pharmaceutical Studies

  • Clorgyline MAO-A inhibitor reduces stereotypy: Pretreating a mouse up to 2 hours with this substance at 0.1mg/kg intraperitoneally prior to methamphetamine administration reduces stereotypy and leads to more locomotor activity across the horizontal plane. As a result of this MAO-A inhibitor, mice will have a delayed onset of stereotypical behavior (increased latency) and will display stereotypies of lower intensity than untreated mice injected with methamphetamine. This effect is observable only at this low dose of clorgyline.
  • GBR 12909 increases route-tracing stereotypy: GBR 12909, also known as vanoxerine, is a selective dopamine reuptake inhibitor that can bind to a dopamine transporter’s target site. When GBR 12909 is given to a mouse at 3 mg/kg, non-significant effects are seen. However, at dosage levels of 10 and 30 mg/kg, mice will have about double the locomotion activity (measured by distance) within their home cages when compared to mice that are given a vehicle solution or 3mg/kg of GBR 12909.

Ulcerative Dermatitis and Pharmaceutical Studies

  • Lithium supplementation increases ulcerative dermatitis incidence: Ulcerative dermatitis has an unknown etiology. But, it may be somehow caused or influenced by the insulin signaling pathway. Lithium acts as an insulin mimetic. A lithium enriched-diet in healthy wild-type mice has been shown to increase their susceptibility to developing ulcerative dermatitis. This indicates that insulin, which lithium mimics, is somehow implicated in the manifestation of ulcerative dermatitis in mice.
  • Maropitant citrate decreases ulcerative dermatitis severity: Maropitant citrate is a tachykinin neurokinin 1 (NK1) receptor antagonist and prevents binding to occur on the NK1 receptor. Substance P (SP) is a neuropeptide that has been linked to the itch-scratch behavior. Administration of maropitant citrate prevents SP from binding to NK1 receptors. Mice that are given 1 mg/kg maropitant citrate will have at least 10% improvement in their lesion size when compared with controls given only water or with mice given 5 mg/kg of the same substance. A significant difference in lesion size is observable after 15 days of treatment. Although the exact mechanism of ulcerative dermatitis remains unknown, it is possible that inhibiting SP binding led to a decrease in the itch sensation which, in turn, reduces scratching behaviors and, ultimately, the skin trauma associated with ulcerative dermatitis.

Mouse Strains Exhibiting Abnormal Behaviors

The different abnormal behaviors will be exhibited by different mouse strains in different ways.

Barbering in Mouse Strains

  • NMRI mice: NMRI mice have been used in behavioral research for almost a century now for general studies as well as for pharmacology or toxicology. NMRI are commonly used as a control or comparator breed but as they increase in age they may develop tumors spontaneously or even renal disease. Social barbering will be exhibited by NMRI mice even if they are housed together since weaning. Social barbering is common in NMRI mice for both males and females. However, in same-sex cages, barbering is also associated with fighting in males, but not in females. If NMRI mice are socially housed together for the first time, barbering will still be observed within 2-5 days of grouping. Barbering within this strain is characterized by head and snout denuding, as well as whisker removal.
  • C57BL/6 mice: C57BL/6 mice will begin to demonstrate social barbering at about 14 weeks of age. At 20 weeks of age, this strain will begin to demonstrate whisker-plucking specifically if housed in pens containing 8 mice or more. In general, C57BL/6 mice are regarded as a strain which demonstrates high levels of barbering and are usually used as a comparator strain in behavioral studies.
  • 129S1 mice: 129S1/SvImJ mice, simply referred to as 129S1 mice, are commonly used as a background strain in behavioral research (as C57Bl/6 mice are) and are known for their anxiety-like behavioral tendencies and learning variabilities. Furthermore, 129S1 mice are also popular in behavioral research as they can be easily used to produce targeted mutations since they have multiple embryonic stem cell lines available. When it comes to barbering, 129S1 female mice are more likely to exhibit social barbering behaviors amongst each other than males under housing conditions, which include group housing since weaning.
  • S-COMT deficient mice: Catechol-O-methyltransferase (COMT) is responsible for catalyzing or breaking down the O-methylation of important catecholic compounds that are found in the brain, such as L-dopa, catecholamines, and also their hydroxylated metabolites. COMT is an enzyme that has two forms, either as soluble (S-COMT) or membrane-bound (MB-COMT) isoforms, but both are known to be products which come from the same gene. In rodents and humans alike, S-COMT is more available, but in the human brain, there is about a 2.5-fold higher amount of MB-COMT than S-COMT. It has been found that mice which lack both forms of COMT have a two-fold increase in the time it takes to eliminate dopamine from the prefrontal cortex. In S-COMT deficient mice, it has been established that subtle social interaction changes occur including increased barbering behavior and decreased sniffing time of another mouse.

Infanticide in Mice

  • C57BL/6J Mice Exhibit High Levels of Infanticide: C57BL/6J mice are known to be highly prone to killing unknown young pups. The degree with which C57BL/6J male mice perform infanticide varies with age, beginning to be significantly more aggressive than other strains when they are as young as 35 days old. The tendency for infanticide significantly lowers when C57BL/6J males are castrated. Similar findings exist for female C57BL/6J mice, averaging a 60% chance of exhibiting infanticide.
  • DBA/2J Mice Exhibit Low Levels of Infanticide: Infanticide is much lower in the DBA/2J male mice than the C57BL/6J male mouse strain. In fact, adult DBA/2J mice, when they are in their prime, kill as many pups as C57BL/6J when they are only 2 months of age. More comparisons need to occur across mouse strains and genders, such as between female DBA/2J and C57BL/6J mice, in order to establish behavioral parameters.

Stereotypies in Mice

  • ICR mice: ICR (CD-1) mice are known to spend prolonged periods of time exhibiting stereotypies with bar-related behaviors such as bar-mouthing. The high tendency for bar-related stereotypies increases with age, peaking in adulthood by taking about 40% of the mouse’s activities. Furthermore, some studies have observed that female mice spend twice as much time as male mice do, climbing on the housing cage lid.
  • C57BL/6 mice: C57BL/6 mice are typically used as comparator mice in stereotypic research. So, this mouse strain does not display a significantly high percentage of excessively repetitive behaviors. Instead, these mice display a normal, rich variety of general activity behaviors like grooming or general locomotion.
  • Down syndrome Ts65Dn mice: Ts65Dn mice are genetic models of Down Syndrome. This mouse strain is known to display stereotypic behaviors. In a litter of about 20 mice, 25% are expected to display repetitive jumping which takes about 22% of their time. About 20% of mice are expected to demonstrate repetitive twirling which takes up about 21% of their time. General stereotypy is expected in about 45% of Ts65Dn mice, compared to about 10% of diploid controls.

Ulcerative Dermatitis in Mice

  • IRs1 deficient mice: Mice which are deficient for the insulin receptor substrate 1 (IRs1) gene have been found to be completely resistant to the development of ulcerative dermatitis. IRs1 is a key component of the insulin-like growth factor-1 (IGF) signaling pathway. Thus, if mice which lack this receptor do not develop ulcerative dermatitis, it indicates that IRs1 may somehow be implicated in the etiology of this inflammatory skin disorder.
  • iNOS deficient mice: Mice which lack the gene of inducible nitric oxide synthase (iNOS) will develop significantly more ulcerative dermatitis when compared to other strains. iNOS-deficient mice have about 50% incidence of ulcerative dermatitis, much higher than the 5% incidence in C57BL/6 strain. Ulcerative dermatitis appears in iNOS-deficient mice around 16 to 20 months of age. iNOS is involved in skin repair. It’s absence and the subsequent high prevalence in ulcerative dermatitis in mice suggests that it may be involved in the etiology of the disease.

Disease Models of Abnormal Behaviors

Barbering Disease Models

NOS2 knockout mice serve as a trichotillomania mouse model. NOS2 knockout mice model trichotillomania and demonstrate high levels of barbering. Trichotillomania is an impulse control disorder which is commonly studied in behavioral research since it is estimated to affect 1-3.5% of the human population. Trichotillomania is characterized by the urge for hair trimming or pulling and can be modeled in mice either through genetic induction or spontaneously. If you’d like to learn more about the trichotillomania mouse models, check out our barbering article.

Infanticide Disease Models

Gabrd−/− Mice Model Postpartum Psychosis. The Gabrd−/− mouse strain is commonly used for modeling postpartum psychosis. In this model, high rates of infanticide are said to be indicative of the disease’s phenotype. Current research is geared towards determining whether this mouse strain may also be used to study postpartum depression.

Stereotypy in Disease Models

Stereotypy can happen spontaneously, if the right genetic model is used, or it can be induced through well-established methods. In this section, we cover the different ways that stereotypy is modeled in behavioral neuroscience research.

Environmentally-Induced Models

Stereotypy can be environmentally-induced. Any stereotypy that manifests as a response to a changed environment is classified as an environmentally-induced stereotypy. Thus, it is possible to manipulate the environment in a controlled fashion in order for mice to develop stereotypy.

Environmentally-induced stereotypies can be achieved through the following experimental approaches:

  • Housing in restrictive cages: Mice that are housed in restrictive and barren cages are very likely to display stereotypic behaviors.
  • Food restriction: Certain mouse strains develop specific stereotypies as a result of food restriction, such as the DBA mouse strain described previously.

Drug-induced Stereotypy Models

In addition to inducing stereotypy through environmental means, it is possible to induce repetitive behaviors also through drug administration. The most commonly used drugs for inducing stereotypy are:

  • Cocaine: Cocaine is used to induce stereotypy in mice. The dosage varies from experiment to experiment, but a dose of 40 mg/kg can significantly increase stereotypy counts in wild-type mice.
  • Methamphetamine: At certain doses, methamphetamine produces stereotypic behaviors such as excessive chewing. Typically, researchers use 10 mg/kg injections of methamphetamine in order to induce stereotypies

For more stereotypy disease models, visit the ethogram page dedicated to Stereotypy.

Ulcerative Dermatitis in Disease Models

High-fat Induced Obesity and Ulcerative Dermatitis

Obesity is induced in mice through a high-fat diet. This also translates to human cases of obesity, since a large proportion is caused due to following a high-fat diet chronically. Some mice that are induced with obesity through a high-fat diet will demonstrate ulcerative dermatitis. Since ulcerative dermatitis can also be caused through a high-fat diet, as mentioned previously, some mice that are used to model obesity are likely to develop this skin inflammation disorder.

Skin Picking Disorder and Ulcerative Dermatitis

Ulcerative dermatitis, as a spontaneously developing skin inflammation condition, is used as a model of skin picking disorder. In humans, skin picking disorder affects about 4% of the general population. Ulcerative dermatitis shares some overlap with skin picking disorder in the following domains: epidemiology, behaviors, and similarity to hair pulling with regards to mechanisms and comorbidity. The relationship between skin picking disorder and ulcerative dermatitis was recently suggested, thus it is a model that is still under scientific scrutiny and in the process of developing.

Do Abnormalities Affect Behavioral Assessment?

Abnormalities, by definition, constitute a range of behaviors that are beyond a mouse’s normal set of behaviors. Thus, abnormal behaviors are bound to have an effect on behavioral assessment.

In fact, most, if not all, abnormal behaviors are bound to have a significant effect on behavioral assessment. For example, mice that display anxiety- or depressive-like behaviors have a significantly different behavioral profile than normal, healthy mice.

The same occurs in mice that have other malfunctional or maladaptive behaviors, such as infanticide.

When abnormal behaviors are observed during an experiment, they must be handled appropriately. Usually, when studying abnormal behavior is not the experimental goal, these mice are removed from the experiment with abnormal behaviors being cited as the reason why.

Summary

  • Abnormal behaviors are a collection of behaviors which are not considered to be normal for a mouse.
  • A behavior can be abnormal and affect a mouse and/or its cagemates on many different dimensions, including physiologically, socially, or psychologically.
  • Abnormal behaviors are classified into malfunction behaviors (abnormal behaviors caused by genetics) and maladaptive behaviors (abnormal behaviors caused by environmental factors).
  • The following behaviors are associated with abnormal behaviors: biting, scratching, jumping, bar-mouthing, circling, route-tracing, chewing, and climbing.
  • The following behaviors are the major types of abnormal behaviors: barbering, self-grooming, infanticide, impulsive/compulsive behaviors, stereotypy, ulcerative dermatitis, depressive-like behaviors, and anxiety-like behaviors.
  • Since abnormal behaviors are considered to be outside the range of normal or acceptable behaviors for a mouse, their function is poorly understood.
  • Depending on the type of abnormal behavior, it may be observed under a variety of situations, including when a mouse: has genetic mutations or physiological issues, is under environmental stress, subjected to laboratory conditions, and is living in group housing.
  • Commonly used research techniques for studying abnormal behaviors include: behavioral studies, pharmaceutical studies, genetic studies, and video recording.
  • The following behavioral tests are used frequently for the purposes of studying abnormal behaviors: the Open Field Test, the Social Interaction Test, the Three-Chamber Test, the Tube Dominance Test, the Resident-Intruder Test, the Parental Behavior test, infrared beams, and rating systems.
  • Pharmaceutical studies have been able to significantly alter abnormal behaviors. The following are some highlights of what pharmaceutical studies have accomplished for the various types of abnormal behaviors:
    • for barbering:
      • clomipramine reduces barbering in trichotillomania mice
      • estradiol injections reduce barbering in trichotillomania mice
    • for infanticide:
      • oxytocin reduces infanticide
    • for stereotypies:
      • clorgyline MAO-A inhibitor reduces stereotypy
      • GBR 12909 increases route-tracing stereotypy
    • for ulcerative dermatitis:
      • lithium supplementation increases ulcerative dermatitis incidence
      • maropitant citrate decreases ulcerative dermatitis severity
    • Abnormal behaviors vary according to mouse strain. Below are some examples of how abnormal behaviors are found from mouse strain to mouse strain:
      • for barbering:
        • Social barbering will be exhibited by NMRI mice even if they are housed together since weaning
        • C57BL/6 mice will begin to demonstrate social barbering at about 14 weeks of age
        • 129S1 female mice are more likely to exhibit social barbering behaviors amongst each other than males
      • for infanticide:
        • C57BL/6J mice exhibit high levels of infanticide
        • DBA/2J mice exhibit low levels of infanticide
      • for stereotypies:
        • ICR (CD-1) mice are known to spend prolonged periods of time exhibiting stereotypies with bar-related behaviors such as bar-mouthing
        • C57BL/6 mice are typically used as comparator mice in stereotypic research
        • Ts65Dn mice are known to display stereotypic behaviors like repetitive jumping or twirling.
      • for ulcerative dermatitis:
        • IRs1 deficient mice are completely resistant to the development of ulcerative dermatitis.
        • iNOS deficient mice have very high levels of ulcerative dermatitis.
      • Abnormal behaviors are modeled in animal research using disease models.
      • To model barbering behaviors, NOS2 knockout mice serve as a trichotillomania mouse model.
      • Gabrd-/- mice model postpartum psychosis and they display infanticide.
      • Stereotypy can be indicted environmentally through food restriction or housing in restrictive cages.
      • Stereotypy can also be induced through drug administration such as cocaine or methamphetamine.
      • Ulcerative dermatitis disease models can be modeled through skin picking disorder and high-fat induced obesity.
      • Abnormalities are known to affect behavioral assessment.

References

  1. http://mousebehavior.org/abnormal-behaviors/
  2. Aizawa, Fuka, et al. “The deletion of GPR40/FFAR1 signaling damages maternal care and emotional function in female mice.” Biological and Pharmaceutical Bulletin 40.8 (2017): 1255-1259.
  3. Atkins, Alison L., et al. “Stereotypic behaviors in mice selectively bred for high and low methamphetamine-induced stereotypic chewing.” Psychopharmacology 157.1 (2001): 96-104.
  4. Bonasera, Stephen J., et al. “A novel method for automatic quantification of psychostimulant-evoked route-tracing stereotypy: application to Mus musculus.” Psychopharmacology 196.4 (2008): 591-602.
  5. 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.
  6. Casarotto, Plinio C., et al. “Inducible nitric oxide synthase (NOS2) knockout mice as a model of trichotillomania.” PeerJ 6 (2018): e4635.
  7. Coleman, Ruth A., et al. “A practical method of chronic ethanol administration in mice.” Alcohol. Humana Press, 2008. 49-59.
  8. Garner, Joseph P., et al. “Barbering (fur and whisker trimming) by laboratory mice as a model of human trichotillomania and obsessive-compulsive spectrum disorders.” Comparative medicine 54.2 (2004): 216-224.
  9. George, Nneka M., et al. “Antioxidant therapies for ulcerative dermatitis: a potential model for skin picking disorder.” PloS one 10.7 (2015): e0132092.
  10. Gross, Alexandra N., et al. “Cage-induced stereotypies, perseveration and the effects of environmental enrichment in laboratory mice.” Behavioural brain research 234.1 (2012): 61-68.
  11. 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.
  12. Horii, Yasuyuki, et al. “Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice.” Scientific reports 7.1 (2017): 6991.
  13. Husk, Sarah Elizabeth Hess. “The role of estrogen in the onset and performance of plucking behavior in a mouse model of trichotillomania.” (2010).
  14. Kalueff, A. V., et al. “Hair barbering in mice: implications for neurobehavioural research.” Behavioural processes 71.1 (2006): 8-15.
  15. 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.
  16. Koh, HY., et al. “Deficits in social behavior and sensorimotor gating in mice lacking phospholipase Cβ1.” Genes, Brain and Behavior 7.1 (2008): 120-128.
  17. 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
  18. McCarthy, Margaret M. “Oxytocin inhibits infanticide in female house mice (Mus domesticus).” Hormones and Behavior 24.3 (1990): 365-375.
  19. Neuhaus, Brit, et al. “Experimental analysis of risk factors for ulcerative dermatitis in mice.” Experimental dermatology 21.9 (2012): 712-713.
  20. Nevison, C. M., J. L. Hurst, and C. J. Barnard. “Why do male ICR (CD-1) mice perform bar-related (stereotypic) behaviour?.” Behavioural Processes 47.2 (1999): 95-111.
  21. Nicholson, Anthony, et al. “The response of C57BL/6J and BALB/cJ mice to increased housing density.” Journal of the American Association for Laboratory Animal Science 48.6 (2009): 740-753.
  22. Sarna, Justyna R., Richard H. Dyck, and Ian Q. Whishaw. “The Dalila effect: C57BL6 mice barber whiskers by plucking.” Behavioural brain research 108.1 (2000): 39-45.
  23. Schmidt, Julia, et al. “Reproductive asynchrony and infanticide in house mice breeding communally.” Animal behaviour 101 (2015): 201-211.
  24. Strozik, E., and M. F. W. Festing. “Whisker trimming in mice.” Laboratory animals 15.4 (1981): 309-312.
  25. Svare, Bruce, et al. “Infanticide: accounting for genetic variation in mice.” Physiology & behavior 33.1 (1984): 137-152.
  26. Svare, Bruce, and Martha Mann. “Infanticide: genetic, developmental and hormonal influences in mice.” Physiology & Behavior 27.5 (1981): 921-927.
  27. Tatsuta, Tomohiro, et al. “Effects of monoamine oxidase inhibitors on methamphetamine-induced stereotypy in mice and rats.” Neurochemical research 30.11 (2005): 1377-1385.
  28. Tur, M. A., and I. V. Belozertseva. “Effect of Spontaneous Partial Sensory Deprivation on the Behavior of Male C57BL/6N Mice.” Neuroscience and Behavioral Physiology(2018): 1-7.
  29. Turner, Cortney A., et al. “Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice.” Behavior genetics 31.4 (2001): 393-400.
  30. Vom Saal, Frederick S., and Lynn S. Howard. “The regulation of infanticide and parental behavior: implications for reproductive success in male mice.” Science 215.4537 (1982): 1270-1272.
  31. Weber, Elin M., et al. “Pup mortality in laboratory mice-infanticide or not?.” Acta Veterinaria Scandinavica 55.1 (2013): 83.
  32. Williams-Fritze, Misty J., et al. “Maropitant citrate for treatment of ulcerative dermatitis in mice with a C57BL/6 background.” Journal of the American Association for Laboratory Animal Science 50.2 (2011): 221-226.
  33. Zafar, Tabassum, and Vinoy K. Shrivastava. “Effect of cold stress on infanticide by female Swiss albino mice Mus musculus: a pilot study.” Journal of animal science and technology 60.1 (2018): 7.

About Maze Engineers

Figuring out the future of neuroscience, one lab mouse at a time.