Definition

Impulsive behaviors are characterized by repeating flexible behaviors that are driven by an inappropriate goal. The behaviors occur at an inappropriate moment and vary across time (i.e. are not frigid repetitions like stereotypy is). Examples of such abnormal behaviors include barbering and binge eating.

Overview

Impulsive behaviors, also referred to as compulsive behaviors, are abnormal behaviors. These behaviors have impulsivity at their core.

Impulsive behaviors are a type of Abnormal Repetitive Behavior (ARB). ARBs are characterized as behaviors that occur in repetition.

In essence, impulsive behaviors do not occur once and then stop. They can be seen in mice multiple times during an observation period.

What Is Impulsivity?

Being able to control behavioral responses is crucial for surviving a dynamic environment. Impulsivity is, simply put, acting without any planning, rational thinking, or foresight. Thus, it is classified as an abnormal behavior.

Furthermore, reward hypersensitization (being overly sensitive to reward) is a key facet of impulsivity.

Recent advances in the study of impulsivity have led to establishing two categories of impulsivity: impulsive action and impulsive choice. This will be discussed in more detail in the next section.

Behavioral researchers are interested in compulsive behaviors because they are ultimately indicative of cognitive abnormalities observed in disease models. For example, impulsivity is a core behavior of addiction and developmental disorders.

Impulsive Action and Impulsive Choice

In order to study and better understand compulsive behaviors, behavioral researchers need to consider two aspects:

  • Impulsive action: Any behavior that describes the behavioral inhibition of a motor response to a stimulus. Impulsive action is also sometimes referred to as “motor impulsivity.” Impulsive actions appear in many different ways, such as the inability to: withhold a response, postpone a response, or stop a response. Thus, increased impulsive action is marked by the inability to stop, withhold, or postpone a particular response.
  • Impulsive choice: A process that is associated with an affective state and/or motivation. In experiments, an impulsive choice is operationalized by observing a mouse’s choice between a small and large reward. Thus, increased impulsive choice behavior can be observed as a preference choice. Impulsive mice go for small and immediate (less effortful) rewards as opposed to delayed, but larger and more beneficial rewards.

Since the processes for impulsive action and impulsive choice are ruled by different neural regions of the brain. By considering these two categories, researchers can consider the different patterns of compulsive behaviors across various psychiatric conditions.

Impulsivity in Humans

In humans, impulsivity can significantly affect everyday life. In fact, deficient inhibitory processes are at the heart of many psychiatric conditions. Addiction, mania, and attention deficit/hyperactivity disorder (ADHD), for example, are all characterized by impulsivity.

Impulsivity vs. Stereotypy in Mice

If impulsivity is the key behavior of the research study, it is important to first rule out motor dysfunction and spontaneous behaviors/stereotypy. Due to their similarities, it is necessary to empirically establish that none of those other factors are confounding. Usually, this behavioral distinction is established via the Elevated Plus Maze and Open Field tests. Once that is done, it is okay to perform all impulsive tests of interest.

Impulsivity and stereotypy are both abnormal behaviors characterized by excessive repetition. But, what separates them? Stereotypy is more rigid and automatic when compared to impulsive behaviors.

Take, for example, barbering, a fur or whisker-plucking behavior that a mouse performs on itself or other mice. If barbering is performed excessively, it is classified as an impulsive/compulsive behavior, not as a stereotypy. Why? Because each instance of plucking behavior is goal-directed and flexible in the way it’s performed but it is abnormal when performed at an inappropriate time.

Related Behaviors

Below is a list of the minor behaviors which are required in order to make the behaviors possible.

  • 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 both comprised of high instances of biting.
  • Grooming: Grooming refers to the cleaning that a mouse does on its (or another mouse’s) fur and body. Grooming behaviors are typically classified as maintenance behavior since they serve to keep a mouse’s appearance, homeostasis, and cleanliness.
  • Novelty seeking: Novelty seeking is the behavioral description of seeking intense and novel sensations and experiences. It is a risk factor for developing impulsivity disorders such as alcoholism.
  • Anxiety-like behaviors: Anxiety-like behaviors are often studied in parallel with impulsivity. This is especially the case when studying alcoholism since anxiety disorders are usually comorbid with them.

Types of Impulsive Behaviors

The following behaviors can be further classified as impulsive behaviors:

  • 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.
  • Binge eating: Binge eating is a feeding behavior where a mouse eats more than the normal amount.
  • Alcoholic drinking: Drinking is also a feeding behavior, but when it is performed in excess, it is a type of impulsivity/compulsive behavior. In experimental studies, genetic links of alcoholism and impulsivity can be investigated.
  • Impulsive aggressive behavior: Aggressive behavior becomes impulsive when it is performed without provocation or a reason and it continuously occurs.

Function

There is no known function of impulsivity. In fact, it is a set of behaviors that are not associated with a clear-cut purpose and may ultimately be harmful.

Application

Impulsivity is triggered by the following factors:

  • Genetic mutations: Impulsive behaviors can be tracked down to specific genetic mutations.
  • Stressful environmental conditions: Not just genetic mutations lead to impulsivity, also stressful environmental factors have been shown to have an effect.
  • Social isolation: Since mice are social creatures, stressful situations like isolation lead to behavioral abnormalities including, but not limited to, impulsivity, aggression, and anxiety.
  • Inactivity: Mice that are inactive and do not exercise have lower impulse control. Thus, higher levels of impulsivity/compulsive behaviors can be observed in inactive mice.
  • 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.

Research Techniques

The following research techniques can be used to study compulsive behaviors:

  • Brain stimulation: If brain areas that are associated with impulsive behaviors and the reward system are stimulated, impulsive behaviors will subsequently be observed. Thus, brain stimulation is a research technique that is quite effective for bringing forth impulsivity.
  • Behavioral studies: Behavioral studies are very useful for studying impulsivity/compulsive behaviors 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 compulsive behaviors. This is done in order to determine how a drug will affect impulsivity. When disease models are the focus of the research, pharmaceuticals are usually used to induce the impulsivity in order to create a model. Or, once impulsivity is significantly higher, drugs are given in an effort to reduce impulsive behaviors.
  • 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 regarding the reasons that a repetitive behavior manifests. These studies may also contain an environmental factor, in order to study the intertwined relationship that genes and the environment have over the development of stereotypies.

Behavioral Tests for Assessing Impulsivity

Behavioral tasks are used to supplement neurological findings, in order to get a better understanding of impulsivity.

Behavioral tests used commonly to assess impulsive action in mice include:

  • 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. 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: This task, also sometimes referred to as discriminatory training, 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). In this task, 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.
  • The five-choice serial reaction time task (5CSRTT): The 5CSRTT is a type of operant conditioning chamber that has a platform with 5 holes/apertures. A mouse is exposed to a light stimulus and it must quickly identify from which hole the light came from in order to receive a sugar reward. Between each trial, there is a short pause where the mouse is expected to withhold any behavioral response. A response during this short interval is considered to be a failure of inhibitory control or, in other words, a sign of impulsivity.
  • Iowa Gambling Task: Using a modified version of the 5CSRTT, the Iowa Gambling Task can be administered to mice in order to measure impulsivity. In this task, mice are trained to use nose-pokes to receive a food reward. Mice are taught to associate the apparatus holes on the left side with “risky” rewards, whereas the apparatus holes on the right side are associated with “safe” rewards.

Behavioral tests used to measure impulsive choice in mice include:

  • The delay-discounting task (DDT): DDT is also sometimes referred to as the delayed-reinforcement task. Delay discounting refers to the process where delayed outcomes, such as postponed food delivery, are valued less than outcomes that are delivered with a short delay or even immediately. To complete this task, mice are given a choice between receiving a 20- or 100-ul drop of milk to be delivered after a 1-second delay. Then, the parameters of the task change and the 100-ul drop of milk is given 100 seconds later. When this delay occurs, mice will demonstrate a preference for the more immediate, but smaller, option. This task is usually administered in an operant chamber, but recent modifications have made it possible to use T-Mazes as well.
  • Effort-discounting tasks: Effort-based decision-making refers to choices that are high in reward but require greater effort as opposed to low-effort decisions that reap small rewards. Similar to the DDT, which was described above, effort-discounting tasks are administered using a T-Maze. A big difference, however, is that effort-discounting tasks include conditions in which a vertical barrier is placed in the maze arm that contains a greater quantity of food. Thus, in order for mice to obtain the larger reward, they must exert a greater effort.

In addition to the above tasks, the following behavioral apparatuses also have been used to study impulsivity in mice:

  • Visual cliff avoidance test: This test measures visual depth perception and the ability to perceive barriers. Mice that have intact vision but still move over the visual cliff are considered to be impulsive.
  • Resident-intruder test: 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.
  • Sucrose preference test: Sucrose preference is frequently used as a measurement in impulsivity tests. Between two dispensary bottles, a mouse can choose between one that has plain water or a sweetened solution.
  • Alcohol preference test: Similar to the sucrose preference test, this measures a mouse’s preference for alcohol. The mouse has a choice between two dispensary bottles, one with water and the other with alcohol. To establish whether a mouse has a propensity to drink, long-term access is given to alcohol.

Pharmaceutical Findings on Impulsive Behaviors

The following findings have been found assessing the effects of pharmaceuticals and chemicals on impulsivity/compulsive behaviors:

Diesel Exhaust Particulate Matter

Chemical exposure to diesel exhaust is a model for environmental ambient particulate matter exposure associated with living in metropolitan areas. Diesel exhaust is used because it is the largest contributor of particulate matter that is airborne.

To assess how particulate matter exposure affects newborn pups, pregnant dams can be  exposed to diesel exhaust. Then, when their offspring reach a suitable age, they can be  subjected to a range of cognitive tests, including cliff avoidance which is a measure of impulsive behavior.

Offspring that are maternally exposed to diesel exhaust particulate matter are ultimately 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. The relationship between air pollution and newborns’ cognitive functioning suggests a critical environmental link.

Prenatal Amphetamine Exposure Increases Impulsivity

Prenatal exposure to psychostimulants can alter executive functions in adult mice. When mice are exposed to psychostimulants like amphetamine or methylphenidate, they demonstrate increased impulsivity and compulsivity in adulthood.

In addition to being more impulsive, these prenatally exposed mice show reward hypersensitization meaning that they have heightened motivation for reward. The impulsivity combined with high motivation (which results from amphetamine or methylphenidate exposure) represents the major symptoms of impulse control disorders and addiction.

Brexpiprazole Reduces Impulsivity

Brexpiprazole is a drug that can influence serotonin levels due to its ability to modulate serotonin-dopamine activity. Brexpiprazole acts as a partial agonist to dopamine D2/3 and 5-HT1A receptors. Furthermore, in the USA, it has recently received approval for treating schizophrenia and adjunctive treatment in major depressive disorder for patients that are not responding well to monotherapy.

When given to mice that model mania due to higher levels of circulating dopamine and exhibit high levels of impulsivity, brexpiprazole reduces impulsive behaviors.

Milnacipran Can Reduce Impulsivity

Serotonin/noradrenaline reuptake inhibitors (SNRI) are a class of drugs commonly used for treating major depressive disorder. However, they have serious side effects, like higher impulsivity and aggression, which are ultimately dangerous risk factors that could lead to criminal involvement and substance abuse. In order to address this dilemma between treatment and serious side effects, milnacipran can be used.

Milnacipran is both an antidepressant and an SNRI, thus it may be able to divert some of the serious side effects associated with SNRIs. In terms of impulsivity, milnacipran diminishes impulsivity in mice as measured by the reduced number of premature responses that occur in a 3CSRTT task.

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. This is also seen in mice where fluoxetine administration ultimately treats aggressive impulsive behaviors.

When non-treated socially isolated mice are introduced to a non-aggressive resident intruder, they react with abnormally high impulsive aggression. However, when socially isolated mice are treated with fluoxetine, aggressive impulsivity is subsequently reduced. Such behavioral findings demonstrate that the serotonergic system, and fluoxetine which acts on this system, are involved in aggressive behaviors.

Ro60-0175 Reduces Premature Responses

Ro60-0175 is a 5-hydroxytryptamine 2C (5-HT2C) receptor agonist. When adult mice are treated with 0.6 mg/kg subcutaneously of Ro60-0175, they show reduced signs of impulsivity in the 5CSRT task as indicated by a drop of premature responses.

SB242084 Increases Premature Responses

SB242084 is a 5-HT2C receptor antagonist. When adult mice are given 0.5 mg/kg of SB242084 intraperitoneally, they exhibit increased premature responses in the 5CSRT task. Thus, this serotonin antagonist has a pro-impulsive effect on mice.

Mouse Strains

Mouse strains are used in research to find the contribution that genetics have in impulsive choice and activity.

C57BL/6J

C57BL/6J mice, since they are the standard comparator strain in behavioral neuroscience research, are also used as a control strain for measuring impulsivity. The C57BL/6J mouse strain is expected to have a premature response rate of about 5%. This is only a little higher than BALB/cJ but lower than CBA/J mice which have about an 8% premature response rate.

However, when it comes to false alarm rates in the Go/No-Go task, C57BL/6 mice are very accurate and demonstrate one of the lowest false response rates, averaging about 25%.

CBA Mice

CBA/J mice are commonly used in behavioral research but are known for their tendency to develop early congenital blindness. These mice usually perform poorly in learning and memory tests, such as the Radial Arm Maze and Morris Water Maze. They also demonstrate relatively high levels of impulsivity. Their premature response rate is about 8% and their rate of false alarms of the Go/No-Go task is about 40%.

A different strain, the CBA/Ca strain is used to study leukemogenesis, the development of leukemia in bone marrow. These mice have some genetic abnormalities that may lead to the development of radiation-induced acute myeloid leukemia, an occurrence that can be seen in humans who have myeloid disorders. Cognitively, CBA/Ca mice have been found to demonstrate less impulsive choice than C57BL/6 mice do.

129/Sv Mice

129/Sv mice, commonly used in behavioral research, are considered to be a relatively hypoactive strain. They also demonstrate a lower rate of impulsive choice when compared to C57BL/6 mice.

C3H/HeJ Mice

The C3H/HeJ mouse strain was established in the 1920s by crossing a Bagg albino and a DBA mouse and is still frequently used by behavioral researchers. Over time, they developed a mutation for Toll-like receptor 4 for which they became known for. These mice are amongst the most impulsive mouse strains. C3H/HeJ mice have been reported to have a high premature responsivity rate by as much as 10%.

When it comes to the Go/No-Go task, this mouse strain has about 50% false alarm response rates. By comparison, C57BL/6 mice average about 25%.

DBA Mice

DBA mice are slightly more impulsive than the C57BL/6J mouse strain. When tested on impulsive choice using the delayed-discounting task, mice are confronted with choosing between small-sized and large-sized rewards. Initially, they receive the reward immediately, but as the task continues, it takes more time to receive the larger reward. Thus, mice naturally shift towards receiving the small-sized reward which occurs faster. Between DBA mice and C57BL/6 mice, the DBA strain is more sensitive towards the increasing delay in receiving the large reward. Due to this sensitivity, DBA mice quickly developed a preference for receiving the small reward. Because of this quick shift of preference, DBA mice turn out to be more impulsive than the C57BL/6 strain.

Serotonin Knockout Mice

Serotonin (5-HT) knockout mice lack one of the key serotonin receptors, namely, the 5-HT1B receptor. Serotonin knockout mice respond to positive reinforcement by acquiring cocaine via self-administration faster and drink more alcohol when compared with wild-type mice. They also show higher levels of impulsive aggression.

Prostaglandin Knockout Mice

Prostaglandins are arachidonic acid metabolites that are involved in physiological and pathophysiological processes.

Ptger1-/- mice (deficient in prostaglandin E receptor subtype EP1)have been found to demonstrate behavioral disinhibition. More specifically, these prostaglandin knockout mice demonstrate impulsive aggression and impaired cliff avoidance.

Heterozygous Reeler Mice

Heterozygous reeler mice are amongst the most impulsive of mouse strains and display high levels of motor impulsivity. As early as adolescence, these mice demonstrate low levels of behavioral disinhibition. Some researchers hypothesize that this issue of motor impulsivity may be due to the strain’s reduced neural plasticity.

Mutant β1 Thyroid Receptor Mice

Transgenic mice with a mutant β1 thyroid receptor (TRβ1) display all behavioral symptoms associated with attention deficit hyperactivity disorder (ADHD). Their behavioral profile includes inattention, hyperactivity, and impulsivity. When tested for impulsivity, TRβ1 mice display poor impulse control when it comes to tasks that measure the delay of gratification.

Dopamine Transporter Knockdown Mice

Dopamine transporter (DAT) knockdown (KD) mice have functional, but reduced levels of DAT. When assessed on their behavior, these mice demonstrate higher levels of risk-taking behavior in the Iowa Gambling Task.

APP-SWE Mice

APP695SWE transgenic mice (APP-SWE) express human amyloid precursor protein (APP) with two-point Swedish mutation.

These mice display high levels of motor impulsivity and are unable to avoid punishment or withhold nose-poking when they are in the waiting interval.

Tau58-2/B Mice

Tau58-2/B mice demonstrate tau pathology in frontotemporal areas. As a result, these mice have increased impulsivity combined with decreased executive functions. This strain also demonstrates decreased social behaviors.

FMR1 KO Mice

Fragile X mental retardation 1 (FMR1) KO mice lack the FMR1 gene and model Fragile X syndrome, a form inherited mental retardation.

FMR1 KO mice have a significantly higher rate of premature responses when compared to control C57BL/6J mice. FMR1 KO mice average about 40% premature responses over 20 sessions while control mice average 30%.

R6/2 Mice

R6/2 mice model Huntington’s disease. When tested for their ability to perform discrimination training, also known as the Go/No-Go task, they demonstrate cognitive deficits. This mouse strain has significant impairment in discrimination acquisition.

zQ175 KI Mice

Huntington’s disease is also modeled by zQ175 KI mice. This mouse strain shows impaired cognition in the discriminatory Go/No-Go task. In this strain, homozygous mice appear to be more cognitively impaired and show greater impulsivity than heterozygous zQ175 KI mice, an observation that’s verging on significant.

Protein Kinase C Gamma Null Mutant Mice

Recent findings have shown that the neuronal-specific γ subtype of protein kinase C (PKCγ) is involved in regulating some behaviors and responses to drinking ethanol. Null mutant PKCγ mice demonstrate a high correlation between ethanol consumption and impulsivity.

Impulsive Behaviors in Disease Models

Modeling impulsivity/compulsive behaviors in mice is important for capturing disease phenotypes, including cognitive characteristics relating to impulsivity.

ADHD

ADHD is a developmental disorder that is characterized by the following cognitive states and behaviors: hyperactivity, inattention, and impulsivity. In humans, ADHD affects multiple parts of everyday life. In mice, ADHD is modeled in many different ways, including by genetic manipulation. Two strains that link impulsivity with ADHD genetics are the DAT KD mice and TRβ1 transgenic mice.

Fragile X Syndrome

As mentioned previously, FMR1 KO mice lack the FMR1 gene and model Fragile X syndrome, a form inherited mental retardation. Due to their genetic makeup,  FMR1 KO mice have impaired cognition.

When compared to control C57BL/6J mice, FMR1 KO mice have a significantly higher rate of premature responses  FMR1 KO average about 40% premature responses over 20 sessions while control mice average 30%.

Specifically, these mice show the highest levels of inhibitory control impairment when exposed to arousing or stressful stimuli.

Addiction Models

Addiction in mice can be modeled environmentally or genetically. Environmentally, mice are given extended access to alcohol, for about 70 days, then alcohol preference and addiction-like behaviors are measured.

Addiction models are of interest to behavioral researchers as they are characterized by compulsive behaviors, ultimately perpetuating addictive behaviors.

Mania

Mania is modeled by DAT knockdown mice which have reduced levels of the dopamine transporter. These mice have hyper-exploratory behavior which is a key behavioral characteristic of mania. These mice also demonstrate higher levels of impulsive behaviors.

Schizophrenia

Schizophrenia can be modeled by Reeler mice. This strain has downregulated reelin, an extracellular matrix protein that is secreted by GABA interneurons. Downregulated reelin protein has been linked to psychiatric disorders, including schizophrenia. Heterozygous reeler mice demonstrate high levels of impulsivity, decreased behavioral inhibition, and altered pain threshold.

Frontotemporal Dementia

Tau58-2/B mice model frontotemporal dementia. These mice have tau pathology in frontotemporal areas. Furthermore, these mice have increased impulsivity combined with decreased executive functions.

Also, Tau58-2/B mice demonstrate heightened arousal to sensory stimuli, a characteristic seen in patients with frontotemporal dementia and Alzheimer’s disease.

Alzheimer’s Disease

Alzheimer’s disease has been associated with impulsive behaviors. APP-SWE transgenic mice that model Alzheimer’s disease have gradually impaired cognition, including hyperactivity and motor impulsivity.

Binge Eating, Overeating, and Obesity

Excessively stimulating the nucleus accumbens leads to reward hypersensitization. In mice, this can lead to abnormally high levels of binge eating. This induction method is currently being investigated for its applicability for modeling binge eating, overeating, and obesity.

Huntington’s Disease

Huntington’s disease is a genetic disorder where the brain’s nerves progressively break down, resulting in fatal consequences. This disease is characterized by gradually increasing, irreversible cognitive deficits and motor impairments.

R6/2 mice and zQ175 KI mice both model Huntington’s disease. When tested for their ability to perform discrimination training, both strains demonstrate high instances of impulsive behaviors.

Do Impulsive Behaviors Affect Behavioral Assessment?

In behavioral research, it is important to establish that mice are not impulsive. This is especially true when characterizing a newly developed genetically modified mouse model’s behavioral phenotype.

Thus, at a minimum, initial behavioral screens include motoric tests of function and activity. Furthermore, additional spontaneous behaviors can be examined using the Elevated Plus-Maze, Open Field, or the Novel Object Test.

Impulsivity affects behavioral assessment because it is a complex psychological construct that can influence a mouse’s behavioral predisposition.

Summary

  • Impulsive behaviors are also known as compulsive behaviors. The terms are interchangeable.
  • Impulsive behaviors are characterized by repeating flexible behaviors driven by an inappropriate goal.
  • Compulsive behaviors are abnormal repetitive behaviors.
  • Impulsivity is, simply put, acting without any planning, rational thinking, or foresight.
  • Recent advances in the study of impulsivity have led to establishing two categories of impulsivity: impulsive action and impulsive choice.
  • In humans, impulsivity can significantly affect everyday life. In fact, deficient inhibitory processes are at the heart of many psychiatric conditions.
  • If impulsivity is the key behavior of the research study, it is important to first rule out motor dysfunction and spontaneous behaviors (stereotypy).
  • Behaviors related to impulsivity (i.e. compulsive behaviors) include: nose-poking, biting, grooming, novelty seeking, and anxiety-like behaviors.
  • Types of impulsive behaviors include barbering, binge eating, alcoholic drinking, and impulsive aggressive behavior.
  • There is no known function of compulsive behaviors.
  • Compulsive behaviors are triggered by the following factors: genetic mutations, stressful environmental conditions, social isolation, inactivity, and age.
  • Research techniques used to study impulsive behaviors include brain stimulation, behavioral studies, pharmaceutical studies, and genetic studies.
  • Behavioral tests used for assessing impulsive action include the stop-signal task, the go/no-go task, the five-choice serial reaction time task, and the Iowa gambling task.
  • The following tests are used to measure impulsive choice: the delay-discounting task and the effort-discounting task.
  • Also, the following behavioral apparatuses have been used to study impulsivity: the visual cliff avoidance test, the resident-intruder test, the sucrose preference test, and the alcohol preference test.
  • The following pharmaceutical findings have been established:
    • offspring neonatally exposed to diesel exhaust particulate matter exposed are more impulsive than non-exposed pups.
    • Prenatal exposure to psychostimulants can alter executive functions in adult mice. When mice are exposed to psychostimulants like amphetamine or methylphenidate, they demonstrate increased impulsivity and compulsivity in adulthood.
    • When given to mice that model mania due to higher levels of circulating dopamine and exhibit high levels of impulsivity, brexpiprazole reduces impulsive behaviors.
    • Milnacipran can reduce impulsivity in mice as measured by the number of premature responses that occur in a 3CSRTT task.
    • When socially isolated mice are treated with fluoxetine, aggressive impulsivity is subsequently reduced.
    • Ro60-0175 is a 5-HT2C is a receptor agonist.When adult mice are treated with 0.6 mg/kg subcutaneously of Ro60-0175, they show reduced signs of impulsivity in the 5CSRT task as indicated by a drop of premature responses.
    • SB242084 is a 5-HT2C is a receptor antagonist. When adult mice are given 0.5 mg/kg of SB242084 intraperitoneally, they exhibit an increase of premature responses in the 5CSRT task.
  • Impulsivity is observed to varying degrees across mouse strains, indicating that a genetic component plays a role:
    • The C57BL/6J mouse strain is expected to have a premature response rate of about 5%.
    • CBA/J mice have a premature response rate of about 8% and their rate of false alarms of the Go/No-Go task is about 40%.
    • 129/Sv mice, commonly used in behavioral research, are considered to be a relatively hypoactive strain. They also demonstrate a lower rate of impulsive choice when compared to C57BL/6 mice.
    • C3H/HeJ mice have been reported to have a high premature response rate by as much as 10%. These mice are amongst the most impulsive mouse strains.
    • DBA mice are slightly more impulsive than the C57BL/6J mouse strain is.
    • Serotonin knockout mice respond to positive reinforcement by acquiring cocaine via self-administration faster and drink more alcohol when compared with wild-type mice
    • Mice that are deficient in prostaglandin E receptor subtype EP1 (Ptger1-/-) have been found to demonstrate behavioral disinhibition
    • Heterozygous reeler mice are amongst the most impulsive of mouse strains and display high levels of motor impulsivity.
    • Transgenic mice with a mutant β1 thyroid receptor (TRβ1) display all behavioral symptoms associated with attention deficit hyperactivity disorder (ADHD), including high impulsivity.
    • Dopamine transporter (DAT) knockdown (KD) mice have functional, but reduced levels of DAT. When assessed on their behavior, these mice demonstrate higher levels of risk taking behavior in the Iowa Gambling Task.
    • APP-SWE mice display high levels of motor impulsivity and are unable to avoid punishment or withhold nose-poking when they are in the waiting interval.
    • Tau58-2/B mice have increased impulsivity combined with decreased executive functions.
    • FMR1 KO mice have a significantly higher rate of premature responses when compared to control C57BL/6J mice.
    • R6/2 mice have a significant impairment in discrimination acquisition.
    • zQ175 KI mice show impaired cognition in the discriminatory Go/No-Go task.
    • Null mutant PKCγ mice demonstrate a high correlation between ethanol consumption and impulsivity.
  • The following disease models have impulsivity as a key behavioral component:
    • ADHD is a developmental disorder that is characterized by the following cognitive states and behaviors: hyperactivity, inattention, and impulsivity. ADHD is modeled by DAT KD mice and TRβ1 transgenic mice.
    • Fragile X syndrome is a form of mental retardation. FMR1 KO mice lack the FMR1 gene and model Fragile X syndrome. When compared to control C57BL/6J mice, FMR1 KO mice have a significantly higher rate of premature responses.
    • Addiction models are of interest to behavioral researchers are they are characterized by compulsive behaviors, ultimately perpetuating addictive behaviors.
    • Mania is modeled by DAT knockdown mice which show high levels of impulsive behaviors.
    • Schizophrenia can be modeled by Reeler mice. Heterozygous reeler mice demonstrate high levels of impulsivity, decreased behavioral inhibition, and altered pain threshold.
    • Tau58-2/B mice model frontotemporal dementia. These mice have increased impulsivity combined with decreased executive functions.
    • APP-SWE transgenic mice that model Alzheimer’s disease have gradually impaired cognition, including hyperactivity and motor impulsivity.
    • Excessively stimulating the nucleus accumbens leads to reward hypersensitization. In mice, this can lead to abnormally high levels of binge eating.
    • Huntington’s disease is characterized by gradually increasing, irreversible cognitive deficits and motor impairments. R6/2 mice and zQ175 KI mice both model Huntington’s disease.

In behavioral research, it is important to establish that mice are not impulsive. This is especially true when characterizing a newly developed genetically modified mouse model’s behavioral phenotype. To establish that no other confounds can explain the impulsivity, a series of motor tests is used.

References

  1. 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.
  2. Bari, Andrea, and Trevor W. Robbins. “Inhibition and impulsivity: behavioral and neural basis of response control.” Progress in neurobiology 108 (2013): 44-79.
  3. 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.
  4. Wu, Hemmings, et al. “Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man.” Proceedings of the National Academy of Sciences 115.1 (2018): 192-197.
  5. Koike, Hiroyuki, et al. “Behavioral abnormality and pharmacologic response in social isolation-reared mice.” Behavioural brain research 202.1 (2009): 114-121.
  6. Binder, Elke, et al. “Regular voluntary exercise reduces anxiety-related behaviour and impulsiveness in mice.” Behavioural Brain Research 155.2 (2004): 197-206.
  7. 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.
  8. Salamone, John D., et al. “Dopamine, effort-based choice, and behavioral economics: basic and translational research.” Frontiers in behavioral neuroscience 12 (2018): 52.
  9. 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.
  10. Lloyd, S. A., et al. “Prenatal exposure to psychostimulants increases impulsivity, compulsivity, and motivation for rewards in adult mice.” Physiology & behavior 119 (2013): 43-51.
  11. Milienne-Petiot, Morgane, et al. “Brexpiprazole reduces hyperactivity, impulsivity, and risk-preference behavior in mice with dopamine transporter knockdown—a model of mania.” Psychopharmacology 234.6 (2017): 1017-1028.
  12. Tsutsui-Kimura, Iku, et al. “Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner.” Journal of pharmacological sciences 134.3 (2017): 181-189.
  13. Koike, Hiroyuki, et al. “Behavioral abnormality and pharmacologic response in social isolation-reared mice.” Behavioural brain research 202.1 (2009): 114-121.
  14. Rithidech, K. Noy, E. P. Cronkite, and V. P. Bond. “Advantages of the CBA mouse in leukemogenesis research.” Blood Cells, Molecules, and Diseases 25.1 (1999): 38-45.
  15. Isles, Anthony R., et al. “Common genetic effects on variation in impulsivity and activity in mice.” Journal of Neuroscience 24.30 (2004): 6733-6740.
  16. 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.
  17. Pinkston, Jonathan W., and Richard J. Lamb. “Delay discounting in C57BL/6J and DBA/2J mice: Adolescent-limited and life-persistent patterns of impulsivity.” Behavioral neuroscience 125.2 (2011): 194.
  18. Brunner, Dani, and Renè Hen. “Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice.” Annals of the New York Academy of Sciences 836.1 (1997): 81-105.
  19. Matsuoka, Yoko, et al. “Prostaglandin E receptor EP1 controls impulsive behavior under stress.” Proceedings of the National Academy of Sciences 102.44 (2005): 16066-16071.
  20. Ognibene, Elisa, et al. “Impulsivity–anxiety-related behavior and profiles of morphine-induced analgesia in heterozygous reeler mice.” Brain research 1131 (2007): 173-180.
  21. Siesser, W. B., et al. “Transgenic mice expressing a human mutant β1 thyroid receptor are hyperactive, impulsive, and inattentive.” Genes, Brain and Behavior 5.3 (2006): 282-297.
  22. Young, Jared W., et al. “Increased risk-taking behavior in dopamine transporter knockdown mice: further support for a mouse model of mania.” Journal of psychopharmacology 25.7 (2011): 934-943.
  23. Adriani, Walter, et al. “Motor impulsivity in APP-SWE mice: a model of Alzheimer’s disease.” Behavioural pharmacology 17.5-6 (2006): 525-533.
  24. Moon, Ji-sook, et al. “Attentional dysfunction, impulsivity, and resistance to change in a mouse model of fragile X syndrome.” Behavioral neuroscience 120.6 (2006): 1367.
  25. Oakeshott, Stephen, et al. “Deficits in a simple visual Go/No-go discrimination task in two mouse models of Huntington’s disease.” PLoS currents 5 (2013).
  26. Bowers, Barbara J., and Jeanne M. Wehner. “Ethanol consumption and behavioral impulsivity are increased in protein kinase Cγ null mutant mice.” Journal of Neuroscience 21.21 (2001): RC180-RC180.
  27. Leo, Damiana, and Raul R. Gainetdinov. “Transgenic mouse models for ADHD.” Cell and tissue research 354.1 (2013): 259-271.
  28. Radwanska, Kasia, and Leszek Kaczmarek. “Characterization of an alcohol addiction‐prone phenotype in mice.” Addiction biology 17.3 (2012): 601-612.
  29. Brunner, Dani, and Renè Hen. “Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice.” Annals of the New York Academy of Sciences 836.1 (1997): 81-105.
Author Details
MazeEngineers makes behavioral mazes for all species with high precision and accuracy. Each maze is hand made for exacting specifications, with automation, AI integration and open software integration. We’re here to build the world’s best behavioral library, we’d love to help you with your experiments. Send us questions and we’ll answer!
×
MazeEngineers makes behavioral mazes for all species with high precision and accuracy. Each maze is hand made for exacting specifications, with automation, AI integration and open software integration. We’re here to build the world’s best behavioral library, we’d love to help you with your experiments. Send us questions and we’ll answer!