Stereotypy

Stereotypy is a general term that refers to any behavior that is performed in excessive repetition without a clear goal.

Stereotypy in mice is characterized by the repetitive movement that is invariant and without a goal.

Stereotypy is a type of abnormal behavior, thus it is not considered to be a normal mouse behavior.

More specifically, stereotypy is an abnormal repetitive behavior (ARB). ARBs are a category of abnormal behaviors in which repetition is characteristic of the mouse’s behavior.

Translatability of Stereotypy to Human Diseases

Stereotyped behaviors have been associated with psychiatric and neurological behaviors. However, clinically speaking, stereotyped behaviors are most commonly linked to developmental disorders like mental retardation and autism.

Stereotypies that have been observed in humans diagnosed with developmental disorders include self-injurious behavior like head banging, head rolling, hand flapping, and body rocking.

However, in mice, stereotypies are typically studied under environmental restriction scenarios or drug-induced paradigms such as pharmacological models which lead to high instances of sniffing , licking, gnawing, and grooming.

Stereotypy and Drug Research

Rodent stereotypy has a long history of being measured and assessed in the field of psychopharmacology. In behavioral research, the term ‘stereotypy’ was first used to describe the physiological effect of stimulant or excitatory drugs like apomorphine or amphetamine.

Scientists in the field of drug research and pharmaceuticals are particularly interested in stereotyped behavior.

Since stereotypy occurs in mice housed under laboratory standards, it is a problem that can affect research results and the quality of research. Stereotypy can be taxing on the laboratory’s resources, thus must be properly managed. Currently, efforts are being made in order to subdue or inhibit the development of stereotypy in laboratory mice. Environmental enrichment, a means of stimulating the brain via immediate physical surroundings, is among the most favorable solutions for reducing and inhibiting the development of stereotypy.

However, enriched caging is not an entire solution for reducing or preventing stereotypy since it is still possible to observe stereotypical behavior such as patterned running under such housing conditions.

The following behaviors are likely to be performed repetitively and to the extreme:

• 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.
• 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.
• 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.
• Self-grooming: When self-grooming is performed in excess, it is considered to be an abnormality because, as a result, the mouse will probably suffer from self-inflicted wounds and lesions.

None. Stereotypical behavior does not serve a function as it is defined to be a repetitive behavior performed without a clear goal.

Stereotypy can be observed under the following conditions:

• Under environmental stress: Environment is another major factor influencing the development of stereotypies in mice. Stressors, like restrictive housing or food restriction, are used to invoke stereotypies in genetically-prone mice like histidine decarboxylase knockout mice or bronx-waltzer mice.
• A mouse has genetic mutations or physiological issues: Many of the stereotypies have been shown to have genetic ties. Although the environment also plays a role in the development of stereotypy, genetic correlations and mutations have been linked to a multitude of repetitive behaviors.

• Behavioral studies: Behavioral studies are very useful for studying stereotypy because they enable the researcher to profile, describe, and quantitatively assess repetitive behaviors across mouse strains and interventions.
• Pharmaceutical studies: Pharmaceutical studies are used when studying the effect of certain drugs or supplements on repetitive behaviors. This is done in order to determine how a drug will affect the manifestation of a stereotypy’s phenotype. Since repetitive behaviors in mice also model diseases that are seen in humans, pharmaceutical studies play a key role.
• Genetic studies: Genetic studies are useful for identifying potential genes involved in the etiology of stereotypy behaviors. Through genetic studies, a better understanding can be gained of the reasons that a repetitive behavior manifests. These studies may also contain an environmental factor, in order to study the intertwined relationship which genes and the environment have over the development of stereotypies.
• Video recording: Video recording is a commonly used technique for studying stereotypy. The reason for this is that videotapes can capture and record behavior, allowing the researcher to observe and count all instances of repetitive behaviors, ultimately reducing the frame of error. This is especially useful since stereotypies occur in rapid succession, making it difficult to quantify all expressed behaviors in real-time.

Measuring Stereotypy: Multiple protocols

Stereotypy can be measured in many different ways, it just depends on what the protocol in place specifies. Typically, if the same movement or sequence is repeated without stop for 3 seconds (such as bar-mouthing) or at minimum three times consecutively for more than 3 seconds without stopping (such as circling, back-flipping, or route-tracing), then that behavior is classified as a stereotypy.

Commonly used windows of observation include observing mice for:

• 60 seconds, every 10 minutes, for a span of 2 hours.
• 60 seconds, every 5 minutes, for 30 minutes.

Stereotypy Behavior Scales

In order to measure stereotypy, it is common to use rating scales. Rating scales quantify the extent and level that stereotypy is displayed during a pre-set observational period.

The first stereotypy rating scale was devised by Creese and Iversen in 1973 in an experiment to assess stimulant-induced stereotypical behavior. Ever since then, this rating scale has been utilized through behavioral research assessing stereotypy. This scale ranges from 0 to 6, as follows:

• 0= or stationary;
• 1= active;
• 2= predominantly active, but with a burst of stereotyped sniffing or rearing;
• 3= stereotyped activity such as sniffing along a fixed path in a cage;
• 4= stereotyped sniffing or rearing maintained in one location;
• 5= stereotyped behavior in one location, with bursts of gnawing or licking; and
• 6= continual gnawing or licking of the cage bars.

Below is another example of a  stereotypy behavior scale :

0= Asleep

1= Awake but still

2= Grooming or mild licking;

3= Continuous locomotion for the duration of 30 seconds along the horizontal plane  without instances of rearing

4= Continuous locomotion for the duration of 30 seconds along the horizontal plane with instances of rearing

5= Bouts of locomotion along the horizontal plane (i.e., darting) without instances of rearing or sniffing

Although rating-scale data can be valid, there are a number of problems associated with the use of such a system:

1. Stereotypy as a behavior vs. descriptor: The use of a rating scale tends to reinforce the notion that stereotypy is a behavior, rather than a descriptor of the behavioral pattern.
2. Subjectivity: Rating scales are subjective by nature, even if the observer is blind to treatment. This subjectivity can contribute greatly to variation between experiments and between laboratories.
3. Has assumptions: An important assumption is that a quantitative rating is acquired as a result of using these rating systems, but the results are not entirely objective, as described in the previous point.

Thus, as discussed in the next section, automated beam detection systems are another possible solution for quantifying stereotypy.

Infrared Beams Quantify Stereotypy

The use of behavioral monitoring systems, such as the SmartCage System, is becoming more and more popular in behavioral neuroscience, especially for studies that focus on stereotypical behavior.

These systems can detect and quantify motion automatically via infrared beams (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.

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 incorrectly registered as a stereotypy when it is not (may occur for behaviors like grooming or nibbling), a problem known as misclassification.

Pharmaceutical studies focus on how stereotypy can be modulated through drug administration.

Methamphetamine-Induced Stereotypy

Methamphetamine is a drug that is known to act as an indirect dopamine receptor agonist. It binds to the dopamine transporter, ultimately reversing the dopamine transport process. In mice, methamphetamine is used as a means of inducing stereotypy. Single injections are administered usually at 10 mg/kg with stereotypical behaviors appearing just 20 minutes after injection.

Clorgyline MAO-A Inhibitor Reduces Stereotypy

Clorgyline is a monoamine-oxidase (MAO)-A inhibitor. 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 of 3mg/kg of GBR 12909.

Lobeline Decreases Methamphetamine-Induced Stereotypy

Lobeline is found in Indian tobacco and is an alkaloid. Lobeline can attenuate stereotypy induced by methamphetamine injections. As mentioned previously, mice that are given one injection of methamphetamine display short-term hyperlocomotion and stereotypical behaviors. However, pretreatment lobeline can decrease the severity of stereotypical behaviors following methamphetamine injections.

Fluoxetine Decreases Stereotypy

The drug fluoxetine is one of the standards for treating obsessive-compulsive disorder (OCD). In deer mice, mice which are a natural model of stereotypy due to their high display of functionless repetitive behaviors, consecutive treatment of fluoxetine (20 mg/kg/day i.p.) for 21 days significantly reduces stereotypic behavior. Control deer mice receiving only saline are expected to display about 3250 counts of stereotypic behavior per hour while deer mice on chronic fluoxetine treatment display about 2300 counts of stereotyped behavior per hour.

Chronic Escitalopram Treatment Reduces Stereotypy

Escitalopram is a serotonin inhibitor that is more potent than fluoxetine. Escitalopram can be administered orally to mice through drinking water at 50 mg/kg/day. After a four-week treatment period, stereotypical behavior significantly decreases in deer mice (a mouse strain characterized for its naturally high levels of stereotypical behavior which also serves as a naturalistic OCD animal model). Such a reduction is visible only after chronic treatment of escitalopram (four-weeks long) and not in sub-chronic treatment (one-week long treatment).

Dizocilpine Maleate (MK-801) Increases Stereotypy

MK-801, also known as dizocilpine maleate, is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which can increase locomotion and stereotypic behaviors in mice. It is also used to model certain schizophrenic symptoms in mice as they are seen in humans. In mice, a dose-dependent relationship is seen in the severity and length of the stereotypy duration. The minimum required dose of MK-801 to observe stereotypy is 0.3 mg/kg. At such a dose, mice will spend 50% of their time doing stereotypical behavior and this pattern will diminish within an hour. This relationship increases and plateaus at a dose of 5.0 mg/kg MK-801. At such a high dose a mouse will perform 100% stereotypy consecutively for about 2.5 hours and then decreasing to 75% stereotypy at the 4-hour mark.

Stereotypy can be observed across many mouse strains, providing clues as to how different genetic components can ultimately contribute to various stereotypical behaviors.

ICR (CD-1) 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.

BTBR T+tf/J Mice

BTBR T+tf/J mice are used as a genetic model of autism spectrum disorders (ASDs). These mice have a unique genetic background with a stable phenotype similar to that present in ASDs. The stereotypies that these mice demonstrate include repetitive bar-mouthing and repetitive self-grooming. Compared to C57BL/6J mice, the way BTBR self-groom involves higher frequencies and duration of: paw licking, head washing, body grooming, leg licking, and tail/genital licking.

Deer Mice

Deer mice  (Peromyscus maniculatus) are known to exhibit various forms of stereotypy. Thus, they are used frequently in behavioral research for the purpose of modeling stereotyped behaviors. Deer mice perform a lot of backward somersaulting or backflipping and jumping. These stereotypical behaviors are observable at postnatal day 20 and are already well developed by postnatal day 30.

C58/J Mice

C58/J mice are genetically related to C57BL/6J mice, but they are significantly different when it comes to behavior. Compared to C57BL/6J mice, C58/J mice have deficits in social approach  and demonstrate increased levels of abnormal repetitive behaviors. C58/J mice jump excessively and have abnormally high levels of backflipping. These stereotypies clearly develop in C58/J mice already by postnatal days 20-21. Furthermore, even C58/J mice express such stereotypies when observed generally for their maternal behaviors .

MECP2 Mice

Mutations in the gene encoding for the methyl-CpG binding protein 2 (MECP2) have been found to result in the manifestation of Rett syndrome, a condition that is the main cause of mental retardation in females with autistic features. Mice that have MECP2 mutations are used to model Rett syndrome. These mice have impaired affiliative behaviors, decreased nest building, and stereotypies. In patients with Rett syndrome, stereotypies are commonly observed in the forms of hand-wringing, waving, or clapping. In MECP2 mice, forelimb stereotypies, i.e. repetitive forepaw use, are the main form of stereotypy displayed.

DBA/2 Mice

DBA/2 (DBA) mice perform environmentally-induced stereotypy when subjected to food restriction for 9 consecutive days. In particular, abnormally high levels of climbing are observed in DBA mice as a response to receiving no food. This response is also observable in C57BL/6 mice when subjected to food-restriction, but the subsequent stereotypy is more severe in DBA mice.

5-HT_2C Receptor KO Mice

Serotonin (5-HT) is involved in OCD and clinical evidence suggests that 5-HT_2C receptors may be involved somehow in compulsive-like repetitive behaviors. 5-HT_2C KO mice, when compared to wild type mice, demonstrate higher levels of chewing-related stereotypies, such as chewing greater quantities of clay chewing plastic-mesh screens.

DAT Knockdown Mutant Mice

Hyper-dopaminergic mutant mice, or mice with too much dopamine, are created using a knockdown mutation of the dopamine transporter gene (DAT). DAT knockdown mice have a 170% increase in dopamine levels in the neostriatum’s extracellular space. These mice demonstrate high levels of self-grooming. Their cephalocaudal grooming patterns are more rigid and repetitive than wild-type mice display which tends to be more flexible. Thus, DAT mice are used to model the rigid stereotypy associated with OCD.

Histidine Decarboxylase Knockout Mice

Histidine decarboxylase (HDC) KO mice are a validated model for a rare genetic form of Tourette syndrome. HDC KO mice do not display stereotypies automatically, but only after exposure to either drugs like d-amphetamine or an acute stressor. After exposure to such stimuli, HDC KO mice demonstrate tic-like stereotypy in terms of grooming, exhibiting higher levels of grooming than wild-type controls.

Bronx-Waltzer Mice

Bronx-Waltzer (bv) mice are a commonly used model of hearing and vestibular dysfunction. These mice also demonstrate repetitive circling behavior, a form of stereotypy. When circling repetitively, bv mice do so in a rapid and continuous fashion. This behavior is triggered and prolonged by a stressor. Circling can be expected in about 70% of bv mice, averaging about 17 full body turns per minute.

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.

Obsessive-Compulsive Disorder

Around the world, the 6-month prevalence of OCD is estimated to be as high as 2.1%. OCD is a psychiatric disorder where the patient exhibits compulsions and obsessions. People with OCD are characterized by a rigid pattern of thought, language, or action.

OCD animal models are used in behavioral research in order to inspect the disease’s biological features and to identify potential treatment options. Currently, OCD models are modeled by mice with a particular genetic background.

As mentioned previously, DAT KO mice and 5-HT_2C mice, as well as deer mice, are commonly used strains for modeling OCD.

Tourette Syndrome

Similar to OCD, Tourette syndrome is characterized by repetitive actions known as tics. Tics are made obvious by several factors, including stress, sleep deprivation, and psychostimulants. However, some rare forms of Tourette syndrome have been linked with genetic mutations. HDC mice, mentioned previously under the ‘Mouse Strains’ sub-section, are used to model a rare form of Tourette which is associated with a mutation in the HDC gene.

Autism Spectrum Disorders

ASDs in humans are characterized by cognitive symptoms such as lower social behaviors, but also by repetitive behaviors, such as hand-flapping. BTBR T+tf/J mice are used as a genetic model of ASDs. The stereotypies that these mice demonstrate include repetitive bar-mouthing and repetitive self-grooming. Compared to C57BL/6J mice, the way BTBR self-groom involves higher frequencies and duration of paw licking, head washing, body grooming, leg licking, and tail/genital licking, indicating that these behaviors are performed in excessive amounts.

Rett Syndrome

Rett syndrome is the main cause of mental retardation in females with autistic features. Mice that have MECP2 mutations are used to model Rett syndrome. Furthermore, these mice have stereotypies, but also impaired affiliative behaviors and decreased nest building. In patients with Rett syndrome, stereotypies are commonly observed in the forms of hand-wringing, waving, or clapping. In MECP2 mice, forelimb stereotypies, i.e. repetitive forepaw use, is the main form of stereotypy displayed

Schizophrenia

MK-801 is a drug used to induce and model certain schizophrenic symptoms in mice as they are seen in humans. MK-801 is an NMDA receptor antagonist. Findings in humans show that NMDA antagonists can mimic schizophrenic symptoms with more fidelity than other alternatives, such as amphetamine.  This drug can increase locomotion and overall stereotypic behaviors in mice

Yes. Mice that have excessive stereotypy levels are considered to be abnormal. Thus, any behavioral assessment that is performed on stereotypical mice is bound to be affected by this condition. In fact, many studies have shown that stereotypy compromises normal cognitive performance and learning. For example, a study by Tanimura et al. showed that stereotypical behaviors in mice are associated with a higher number of errors in a T-Maze reversal learning task. Thus, behavioral assessments using stereotypical mice should be conducted carefully and only if that’s a part of the protocol. Otherwise, research results run the chance of receiving unwanted influence from stereotypical behaviors.

1. Garner, Joseph P. “Stereotypies and other abnormal repetitive behaviors: potential impact on validity, reliability, and replicability of scientific outcomes.” ILAR journal 46.2 (2005): 106-117.
2. 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.
3. Volchegorskii, I. A., et al. “Effects of Derivatives of 3-Hydroxypyridine and Succinic Acid on Stereotypical Behavior and Catalepsy in Mice.” Neuroscience and Behavioral Physiology 48.8 (2018): 947-953.
4. Kelley, Ann E. “Measurement of rodent stereotyped behavior.” Current protocols in neuroscience 4.1 (1998): 8-8.
5. Tatsuta, Tomohiro, et al. “Effects of monoamine oxidase inhibitors on methamphetamine-induced stereotypy in mice and rats.” Neurochemical research 30.11 (2005): 1377-1385.
6. 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.
7. Tatsuta, Tomohiro, et al. “Lobeline attenuates methamphetamine-induced stereotypy in adolescent mice.” Neurochemical research 31.11 (2006): 1359-1369.
8. Wolmarans, De Wet, et al. “Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of obsessive-compulsive disorder (OCD): Response to escitalopram treatment and basal serotonin transporter (SERT) density.” Behavioural brain research 256 (2013): 545-553.
9. Wu, Jinhua, et al. “Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice.” Psychopharmacology 177.3 (2005): 256-263.
10. 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.
11. Turner, Cortney A., et al. “Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice.” Behavior genetics 31.4 (2001): 393-400.
12. Pearson, B. L., et al. “Motor and cognitive stereotypies in the BTBR T+ tf/J mouse model of autism.” Genes, Brain and Behavior 10.2 (2011): 228-235.
13. Tanimura, Yoko, Mark C. Yang, and Mark H. Lewis. “Procedural learning and cognitive flexibility in a mouse model of restricted, repetitive behaviour.” Behavioural brain research 189.2 (2008): 250-256.
14. Korff, Schaun, Dan J. Stein, and Brian H. Harvey. “Cortico-striatal cyclic AMP-phosphodiesterase-4 signalling and stereotypy in the deer mouse: attenuation after chronic fluoxetine treatment.” Pharmacology Biochemistry and Behavior 92.3 (2009): 514-520.
15. Ryan, Bryce C., et al. “Social deficits, stereotypy and early emergence of repetitive behavior in the C58/J inbred mouse strain.” Behavioural brain research 208.1 (2010): 178-188.
16. Moretti, Paolo, et al. “Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome.” Human molecular genetics 14.2 (2004): 205-220.
17. 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.
18. Chou-Green, Jennifer M., et al. “Compulsive behavior in the 5-HT2C receptor knockout mouse.” Physiology & behavior 78.4-5 (2003): 641-649.
19. Berridge, Kent C., et al. “Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette’s.” BMC biology 3.1 (2005): 4.
20. Xu, Meiyu, et al. “Histidine decarboxylase knockout mice, a genetic model of Tourette syndrome, show repetitive grooming after induced fear.” Neuroscience letters 595 (2015): 50-53.
21. Ishiguro, Akio, Masumi Inagaki, and Makiko Kaga. “Stereotypic circling behavior in mice with vestibular dysfunction: asymmetrical effects of intrastriatal microinjection of a dopamine agonist.” International Journal of Neuroscience 117.7 (2007): 1049-1064.
22. 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.
23. 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.
24. Tilley, Michael R., and Howard H. Gu. “Dopamine transporter inhibition is required for cocaine-induced stereotypy.” Neuroreport 19.11 (2008): 1137.
25. 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.
26. Chou-Green, Jennifer M., et al. “Compulsive behavior in the 5-HT2C receptor knockout mouse.” Physiology & behavior 78.4-5 (2003): 641-649.
27. Berridge, Kent C., et al. “Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette’s.” BMC biology 3.1 (2005): 4.
28. Tanimura, Yoko, Mark C. Yang, and Mark H. Lewis. “Procedural learning and cognitive flexibility in a mouse model of restricted, repetitive behaviour.” Behavioural brain research 189.2 (2008): 250-256.

• Stereotypy is a general term that refers to any behavior that is performed in excessive repetition without a clear goal.
• Stereotypy is a type of abnormal behavior.
• In mice, stereotypies are typically studied under environmental restriction scenarios or drug-induced paradigms such as pharmacological models which lead to high instances of sniffing, licking, gnawing, and grooming.
• Environmental enrichment is among the most favorable solutions for reducing and inhibiting the development of stereotypy.
• The following behaviors are likely to be performed repetitively and to the extreme: jumping, chewing, bar-mouthing, circling, route-tracing, climbing, and self-grooming.
• Stereotypical behavior does not serve a function as it is defined to be a repetitive behavior performed without a clear goal.
• Environmental stress and genetic mutations are triggers which ultimately lead to stereotypy.
• The following research techniques can be applied to studying stereotypy: behavioral studies, pharmaceutical studies, genetic studies, and video recording.
• Stereotypy can be measured in many different ways, it just depends on what the protocol in place specifies.
• Behavioral scales are used to score a mouse’s level of stereotypy.
• The use of behavioral monitoring systems, such as the SmartCage System, is becoming more and more popular in behavioral neuroscience, especially for studies that focus on stereotypical behavior.
• The following pharmaceutical findings have been established:
  • Methamphetamine administration can induce stereotypy.
  • MAO-A inhibitor reduces stereotypy.
  • GBR 12909 increases route-tracing stereotypy.
  • Lobeline decreases stereotypy induced by methamphetamine administration.
  • Fluoxetine decreases stereotypy.
  • Chronic escitalopram treatment reduces stereotypy.
  • MK-801 increases stereotypy.
• Across various mouse strains, the following findings on stereotypy have been established:
  • ICR mice are known to spend prolonged periods of time exhibiting stereotypies with bar-related behaviors such as bar-mouthing.
  • C57BL/6 mice do not display a significantly high level of excessive behaviors, thus they are often used as comparator mice in research.
  • Ts65Dn mice are expected to display general stereotypy.
  • BTBR mice demonstrate repetitive bar-mouthing and repetitive self-grooming.
  • Deer mice perform a lot of backward somersaulting or backflipping and jumping.
  • C58/J mice jump excessively and have abnormally high levels of backflipping.
  • In MECP2 mice, forelimb stereotypies, i.e. repetitive forepaw use, are the main form of stereotypy displayed.
  • DBA mice have abnormally high levels of climbing as a response to receiving no food.
  • 5-HT_2C KO mice, when compared to wild type mice, demonstrate higher levels of chewing-related stereotypies.
  • DAT KO mice demonstrate high levels of self-grooming.
  • HDC KO mice do not display stereotypies automatically, but only after exposure to either drugs like d-amphetamine or an acute stressor.
  • Bronx-Waltzer mice demonstrate repetitive circling behavior.
• Stereotypy can be environmentally-induced through food restriction or restrictive housing.
• Repetitive behaviors are also inducible through drug administration like cocaine and amphetamine.
• The following disease models have stereotypies as one of their main behavioral characteristics: OCD, Tourette syndrome, ASDs, Rett syndrome, and Schizophrenia.
• Any behavioral assessment that is performed on stereotypical mice is bound to be affected by this condition.