Behaviors

Modeling Impulsive Behavior In Mice

By October 24, 2017 No Comments

A hallmark of our species is the ability to make decisions based on reason and logical thinking. Hundreds of choices bombard us every day, and without the rational decision-making computations our minds are capable of, negative outcomes would dominate. Choosing to stick to decisions and actions that are absent in the rational process of the mind leads to impulsive behaviors.

Impulsivity, then, is acting without any foresight, planning, or rational thinking[1]. Impulsive behavior is disabling to normal daily functioning. Being impulsive, or making impulsive choices and decisions often have negative consequences. The individual may do poorly at school, work, social events, and personal relationships. Impulsive behavior is evident across several psychiatric disorders, such as ADHD, schizophrenia, mania, and addiction[2]. Because impulsivity is a strong component of several psychiatric disorders, research has sought to shed light on the neural and behavioral components of impulsive behaviors.

It’s important to have a good measurement of impulsivity especially when animal models are involved. There are batteries of behavioral tests that can measure impulsivity, but research has shown that specific tests may help provide specific therapeutic treatments within human context. Thus, animal models of impulsivity are established as a medium for potential therapeutic outcomes.

Below, we will discuss how research establishes certain guidelines to evaluate whether or not an experimental mouse is impulsive or not, while also showing some arrays of behavioral tests used to evaluate impulsivity.

What is Impulsivity?

Despite the traditional definition of impulsivity, which consists of behaviors or actions without foresight, a more detailed description of the phenomena has surfaced. There are two categories when it comes to impulsive behavior; impulsive action and impulsive choice.

Impulsive action is defined as the ability to withhold a motor response, by either stopping or simply withholding[2]. This subcategory of impulsivity can be observed among a spectrum of psychiatric disorders. It is prevalent among eating disorders and ADHD, for example. A person’s inability to otherwise control a number of food intake results in poor impulsive action, leading to binge eating and consequently to what we call eating disorder. The same applies to ADHD patients. The difficulty to remain still, silent, and attentive at appropriate times further supplements the role of impulsive action among a range of disorders.

Impulsive choice on the other hand, is defined as a process by which motivational forces affect the choosing of rewards based on quantity, time delay, and effort[2]. Thus choosing a reward that is small, quick and least effortful, points towards impulsive behavior. This subcategory can be observed in cases such as addiction. The repetitive behavior witnesses in addiction, of all sorts, illustrates how small yet immediate rewards will always satisfy a person suffering from the mental disorder. An addictive gambler realizes the potential to lose money in the long run, yet he or she still gambles because the immediate reward, however small, is still satisfactory. Nevertheless, given the complexity of impulsivity and its role in mental illness, research has turned towards investigating possible ways to measure these factors in the lab

The significance of these two sub-categories is illustrated by the behavioral tests used to evaluate them. Impulsive action and impulsive choice are processes governed by different neuronal regions, which affect how research can produce impulsive behavioral models in mice[3]. The subcategories allow researchers to investigate different patterns along with several psychiatric disorders, which can allow for better therapeutic outcomes. Hence it is necessary that pre-clinical experiments test and measure both these categories to the fullest extent.

Modeling Impulsivity in Mice

Producing mice with impulsive behaviors can be done in several ways. Genetically altered mice that mimic psychiatric disorders are one way of reproducing impulsive behaviors in mice. Disorders such as those mentioned above are examples of diseases that exhibit impulsivity. A second, more cost-effective method is by altering the neurotransmitter dopamine. Research has shown that pharmacological substance that lower dopamine levels alter impulsive action and impulsive choice in mice[3].

Because genetic and neuronal alterations may affect other components of the subject, several pre-model examinations are necessary to rule out unwanted behaviors. Motor dysfunction and spontaneous behaviors are two common factors that are necessary to evaluate before performing impulsive tests. Any form of motor delay or deficit must be excluded from the experiment. Likewise, spontaneous behaviors such as anxiety are assessed using several tests, including the open field test and the elevated plus maze.

Measuring Impulsive Action in Mice Model

After initial manipulation of the experimental mouse, i.e. genetic or pharmaceutical, researchers can begin to investigate impulsivity. Recall that impulsive actions are actions that are difficult to control or suppress, and are mistimed. To evaluate this subcategory of impulsiveness, researchers use three main tests.

  1. The five-choice serial reaction time task (5-CSRT).
  2. The stop-signal task (SST).
  3. The go/no-go task.

The 5-CSRT test is used to differentiate among the different genetic mutations that contribute to impulsive action in experimental mice. The test consists of a platform with five locations, and a stimulus is presented at one of these locations. Response must be delayed until a signal comes on that gives permission for action. The higher the response times before permission, the higher the impulsivity.

The other operant tests, SST and go/no-go task, measure the ability to inhibit a response. In the SST, a motor response is initiated by a go signal. During initiation of response, reaction times are measured. On some trials, a stop signal is presented, and researchers measure the time needed to inhibit motor response. The longer it takes the subjects to initiate a stop response, the poorer the inhibitory control they possess.

The go/no-go task is very much like the SST, yet only one signal is given per run. Because go signals dominate in quantity over the no-go signals, mice become primed to initiate motor response. Thus, the higher amount of no-go signal response, the poorer the inhibitory control.

Modeling Impulsive Behavior In Mice

Measuring Impulsive Choice in Mice Model

Impulsive choice, as noted earlier, relies on two important factors, effort and time delay. Impulsive choice tests determine the level of impulsivity in mice by evaluating how each subject responds to rewards based on the manipulation of time and effort. There are two main tests that cover this subcategory of impulsivity:

  1. The delay-discounting task (DDT).
  2. Effort discounting tasks (EDT).

In the delay-discounting task, experimental mice must choose between a small reward given immediately and a larger reward given after some time delay. The variable in this case, time, is changed in both immediate and delay trials, until both options are chosen equally, i.e. reaching an indifference point. This is then done several times until a hyperbolic curve is established. The steepness of the curve determines the level of impulsivity, in which the steeper the curve, the higher the impulsive choice[3].

Likewise, the steps are all the same in the effort discounting tasks, except for the variable, which in this case is represented by effort. Experimental mice have the option to obtain a small reward with the least amount of effort, or a larger reward that requires some form of effort. Again, after repeating the steps, a hyperbolic curve will determine the level of impulsivity. The steeper the curve, the lower the effort exerted by mice to obtain a larger reward[3].

The above measurements have led researchers into getting insight on the neural and anatomical functions of impulsivity. Different measurements witnessed among impulsive action and choice through psychiatrically induced mice can help determine the path to a better therapeutic outcome. Knowing which mental illness possess the most impulsive action versus impulsive choice can help set defining lines into the ways we approach the disorder. Further investigation is necessary to allow studies the ability to translate results from pre-clinical settings into human clinical settings.

Reference

  1. Daniel, T. O., Stanton, C. M., & Epstein, L. H. (2013). The Future Is Now. Psychological Science,24(11), 2339-2342. doi:10.1177/0956797613488780
  2. Dent, C. L., & Isles, A. R. (2014). An Overview of Measuring Impulsive Behavior in Mice. Current Protocols in Mouse Biology,35-45. doi:10.1002/9780470942390.mo140015
  3. D’Amour-Horvat, V., & Leyton, M. (2014). Impulsive actions and choices in laboratory animals and humans: effects of high vs. low dopamine states produced by systemic treatments given to neurologically intact subjects. Frontiers in Behavioral Neuroscience, 8, 432. http://doi.org/10.3389/fnbeh.2014.00432

About Seyed Ahmad

Seyed Ahmad Pour Hakimi graduated from the American University of Beirut with a B.A in Psychology, and is currently pursuing his medical education in Europe. Parallel to his studies, he is conducting research for his book on cardiomyopathies and heart failure, investigating the most efficient and effective therapeutic approach in treating cardiovascular disease. Seyed Ahmad enjoys mixing writing and science to promote scientific literacy and is an active science writer on various topics including neuroscience, medicine, and nutrition.