Name: three laboratory procedures for assessing different manifestations of impulsivity in rats
Uploaded: 2019-03-17T13:00:00
Description: Watch this Scientific Journal Video about Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats at JoVE.com

We would like to thank Florencia Mata, Mar&#237;a Elena Ch&#225;vez, Miguel Burgos, and Alejandro Tapia for providing technical assistance. We also wish to thank Sarah Gordon Frances for her useful comments on a previous draft of this article and Vladimir Ordu&#241;a for kindly providing raw data from a published paper. Thanks to Claudio Nallen for creating the diagram in Figure 1. We are grateful to the Direcci&#243;n de Investigaci&#243;n of the Universidad Iberoamericana Ciudad de M&#233;xico for funding proofreading/editing services and the video producing expenses.

The three protocols described in this section require the use of rats as subjects. Most laboratory rat strains are suitable; for example, Wistar, Long-Evans, Sprague-Dawley, etc. The Ethics Committee of the Universidad Iberoamericana, following the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council, 1996), approved the laboratory protocols to be described.
1. Animal Housing and Preparation
<ol>
	<...

The present article provided a description of a miscellaneous variety of protocols for screening impulsivity in rats. It is argued that these particular protocols are favored for their ease of programming and data analysis and require fewer operating and stimulus devices than other available alternatives. There are several crucial steps for the effective implementation of these protocols, such as (1) yielding a research question, (2) selecting an appropriate study design, (3) programming the selected protocol, (4) conduc...

Impulsivity can be conceptualized as a behavioral dimension associated with maladaptive outcomes1. Despite the widespread use of this term, there is no universal consensus on its precise definition. In fact, several authors have defined impulsivity by giving examples of impulsive behaviors or their consequences, rather than delineating which distinctive aspects govern the phenomenon. For instance, impulsivity is assumed to involve an inability to wait, plan, inhibit prepotent behaviors, or an insensitivity to delayed outcomes2, and it has been considered a core vulnerability to addictive behavior3. Bari and Robbins4 have characterized impulsivity as the co-occurrence of strong impulses, being triggered by dispositional and situational variables, and dysfunctional inhibitory processes. A different definition was provided by Dalley and Robbins, who stated that impulsivity could be regarded as a predisposition to rapid, often premature, actions without appropriate insight5. Yet, another definition of impulsivity, proposed by Sosa and dos Santos6, is a behavior tendency that deviates an organism from maximizing available rewards due to the acquired control exerted over the organism&#39;s responding by stimuli incidentally related to those rewards.
Due to the behavioral processes related to impulsivity, its neurophysiological substrate involves structures in common with those of motivated behavior, decision making and reward valuing. This is supported by studies that show that structures of the cortico-striatal pathway (e.g., nucleus accumbens [NAc], prefrontal cortex [PFC], amygdala, and caudate putamen [CPU]), as well as the ascending monoaminergic neurotransmitter system, participate in the expression of impulsive behavior7. However, the neural substrate of impulsivity is more complex than that. Although NAc and PFC are involved in impulsive behavior, these structures are part of a more complex system, and also are composed by substructures that have different functions (for more detailed documentation, see Dalley and Robbins5).
Regardless of the controversies about its nature and biological substrate, this behavioral dimension is known to vary across individuals, in which case it can be considered as a trait, and within individuals, in which case it can be considered as a state8. Impulsivity has long been recognized as a feature of some psychiatric conditions, such as attention-deficit/hyperactivity disorder (ADHD), substance abuse, and manic episodes9. There seems to be a high consensus that impulsivity is composed by multiple dissociable factors, including unwillingness to wait (i.e., delay discounting), incapacity to refrain prepotent responses (i.e., inhibitory deficit), difficulty to focus on relevant information (i.e., inattention), and a tendency to engage in risky situations (i.e., sensation seeking)5,10,11. Each of these factors can be assessed through special behavioral tasks, which are usually assigned to two broad categories: choice and response inhibition (these may have different labels between each authors&#39; taxonomies). Some important features of such behavioral tasks are that they could be applied across several animal species2&#160;and that they allow&#160;studying impulsivity in controlled laboratory conditions.
Modeling a behavioral dimension with laboratory non-human animals has a number of advantages including the possibility of measuring specific, operationalized behavioral tendencies, allowing the researchers to largely reduce confounding variables (e.g., contamination by past life events4) and to implement experimental manipulations such as chronic pharmacological administration, performing neurotoxic lesions, or genetic manipulations. Most of these protocols have analogue versions for humans, which make comparisons easy5. Importantly, using analogues of these laboratory protocols in humans is effective to aid diagnosis of psychiatric conditions, such as ADHD (especially when more than one protocol is applied12).
Like any other psychological measurement, laboratory protocols for assessing impulsivity must comply with particular criteria in order to achieving the goal of providing insight into the phenomenon under study. To be considered as an appropriate model of impulsive behavior a laboratory protocol should be reliable, and possess (at least, in some degree) face, construct, and/or predictive validity13. Reliability could imply either that an effect upon the measurement would replicate if a manipulation is conducted two or more times, or that the measurement is consistent over time or across different situations14,15. The former feature would be especially useful for experimental studies, while the latter would be so for correlational studies14. Face validity refers to the degree in which what is measured resembles the phenomenon that is supposed to be modeled, as to being, for example, affected by the same variables. Predictive validity refers to the ability of a measure to forecast future performance in protocols, which aim to measure the same or a related construct. Finally, construct validity refers to whether the protocol reproduces behavior that is theoretically sound regarding the process or processes assumed to be involved in the phenomenon under study. However, although these are highly desirable features, one should be cautious when stating that a protocol is valid purely based on these criteria16.
There are several protocols to measure impulsivity in laboratory settings. However, the present article presents only three such methods: intertemporal choice, differential reinforcement of low rates, and feature-negative discrimination. Intertemporal procedures aim to assess the delay discounting (i.e., the difficulty of delayed outcomes to control behavior) component of impulsivity. The basic rationale of this protocol is confronting subjects with two rewards that differ in both magnitude and delay17. One alternative provides a small immediate reward (termed smaller sooner, SS) and the other provides a larger but delayed reward (termed larger later, LL). The proportion of responses to the SS alternative can be used as an index of impulsivity18. In differential reinforcement of low rates procedures, the factor of impulsivity to be assessed is response inhibition (i.e., incapacity to withhold prepotent responses) when there is a negative punishment contingency upon inappropriate responding. The rationale of this protocol is introducing subjects to a situation in which the only way of obtaining rewards is to pause their responding19. Finally, feature-negative discrimination procedure evaluates response inhibition when there is no explicit punishment upon inappropriate responding. The rationale of this protocol (also known as Pavlovian conditioned inhibition or the A+/AX- procedure) is to evaluate subjects&#39; ability to withhold unnecessary responses20.
These procedures stand out in comparison to others as having some convenient features. For example, the procedures presented here are suitable for being conducted in minimally equipped conditioning chambers (also known as &#39;the Skinner box&#39;). Figure 1 shows a diagram of a typical conditioning chamber. Conditioning chambers are useful research instruments due to a number of advantages. They allow automated collection of a relatively large volume of data, maximizing the number of subjects assessed for unity of time and space21. Moreover, behavioral studies conducted in conditioning chambers require minimal researcher intervention, which reduces the time and effort invested by laboratory staff, unlike other available methods (e.g., non-automated T-mazes, set-shifting boxes)21. Minimizing researchers&#39; intervention also help in reducing researchers&#39; bias, decreasing effects of researchers&#39; learning curve, and a reduction of handling-induced stress22. Typical conditioning chambers are fairly standardized to be used with medium sized rodents, such as rats (R. norvegicus), but can be employed to study other taxa, like similar-sized marsupials (e.g., D. albiventris, and L. crassicaudata23). There are also commercial conditioning chambers adapted for smaller (e.g., mice [M. musculus]) and larger (e.g., non-human primates) species. Setting up and conducting the protocols presented in this article require minimal programming skills and demand a quite low number of attainable input and output devices, unlike more sophisticated alternative methods (e.g., 5-choice serial reaction time task [5-CSRTT]24 and sign-tracking25).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/59070/59070fig1.jpg" /> 
Figure 1: Diagram of a conditioning chamber prototype. The main components of the conditioning chamber include: (1) left lever, (2) food receptacle (equipped with lateral infrared diodes to detect head entries), (3) focalized light, (4) speaker for tone emission (rear view), (5) house light (rear view), (6) food dispenser. <a href="https://www.jove.com/files/ftp_upload/59070/59070fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

<table border="0" cellpadding="0" cellspacing="0" style="width:663px;" width="663">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:216px;">25 Pin Cables</td>
			<td style="width:161px;">Med Associates</td>
			<td style="width:119px;">SG-213F</td>
			<td style="width:167px;">Connect smart control cards to smart control panels</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">40 Pin Ribbon Cable</td>
			<td>Med Associates</td>
			<td>DIG-700C</td>
			<td>Connects the computer with the interface cabinet</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Computer</td>
			<td>Dell Computer Company</td>
			<td>T8P8T-7G8MR-4YPQV-96C2F-7THHB</td>
			<td>For controlling and monitoring protocols&#8217; processes</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Conductor Cables</td>
			<td>Med Associates</td>
			<td>SG-210CP-8</td>
			<td>Provide power to the smart control panels via the rack mount power supply</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Food dispenser with pedestal</td>
			<td>Med Associates</td>
			<td>ENV-203M-45 (12937)</td>
			<td>Silently provides 45 mg food pellets&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Head-Entry Detector</td>
			<td>Med Associates</td>
			<td>ENV-254-CB</td>
			<td>Uses an infrared photo-beam to detect head entries into the food receptacle</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">House Light</td>
			<td>Med Associates</td>
			<td>ENV-215M</td>
			<td>For providing&#160; diffuse illumination inside the chamber&#160;&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Interface Cabinet</td>
			<td>Med Associates</td>
			<td>SG-6080D</td>
			<td>Pod that can hold up to eight smart control cards</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Med-PC IV Software</td>
			<td>Med Associates</td>
			<td>SOF-735</td>
			<td>Translate codes into commands for operating outputs and recording/storing input information</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Multiple tone generator&#160;</td>
			<td>Med Associates</td>
			<td>ENV-223 (597)</td>
			<td>For controlling the frequency of the tones</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Panel fillers</td>
			<td>Med Associates</td>
			<td>ENV-007-FP</td>
			<td>For filling modular walls when devices are not used</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Pellet Receptacle</td>
			<td>Med Associates</td>
			<td>ENV-200R2M</td>
			<td>Receives and holds food pellets delivered by the dispenser</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Rack Mount Power Supply</td>
			<td>Med Associates</td>
			<td>DIG-700F</td>
			<td>Provides power to the interface cabinet</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Retractable Lever</td>
			<td>Med Associates</td>
			<td>ENV-112CM (10455)</td>
			<td>Detects lever-pressing responses; projects into the chamber or retracts as needed</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Smart Control Cards</td>
			<td>Med Associates</td>
			<td>DIG-716</td>
			<td>Controls up to eight inputs and four outputs of a conditioning chamber&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Smart Control Panels</td>
			<td>Med Associates</td>
			<td>SG-716 (3341)</td>
			<td>Connect smart cards to the devices within the conditioning chambers</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Speaker&#160;</td>
			<td>Med Associates</td>
			<td>ENV-224AM</td>
			<td>For providing tones inside the chamber</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Standard Modular Chambers for Rat</td>
			<td>Med Associates</td>
			<td>ENV-008</td>
			<td>Made of aluminum channels designed to hold modular devices&#160;</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Standard sound-, light-, and temperature isolating shells</td>
			<td>Med Associates</td>
			<td>ENV-022MD</td>
			<td>Serve to harbor each conditioning chamber</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Stimulus Light</td>
			<td>Med Associates</td>
			<td>ENV-221M</td>
			<td>For providing a round focalized light stimulus</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Three Pin Cables</td>
			<td>Med Associates</td>
			<td>SG-216A-2</td>
			<td>Connects smart control panel with each of the input and output devices in the conditioning chambers</td>
		</tr>
	</tbody>
</table>

three laboratory procedures for assessing different manifestations of impulsivity in rats

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is a meaningful concept because it is associated with psychiatric conditions in humans and with maladaptive behavior in non-human animals. It is believed that impulsivity is composed of separate factors. There are laboratory protocols devised to assess each of these factors using standardized automated equipment. Delay discounting is associated with the incapacity to be motivated by delayed outcomes. This factor is evaluated through intertemporal choice protocols, which consist&#160;of presenting the individual with a choice situation involving an immediate reward and a larger but delayed reward. Response inhibition deficit is associated with the incapacity to withhold prepotent responses. Differential reinforcement of low rates (DLR) and feature-negative discrimination protocols assess the response inhibition deficit factor of impulsivity. The former imposes a condition to a motivated individual in which most wait a minimum period of time for a response to be rewarded. The latter evaluates the capacity of individuals to refrain from food seeking responses when a signal of the absence of food is presented. The purpose of these protocols is to construct an objective quantitative measure of impulsivity, which serves to make cross-species comparisons, allowing the possibility of translational research. The advantages of these particular protocols include their easy set-up and application, which stems from the relatively small amount of equipment needed and the automated nature of these protocols.

The three protocols described in this article may be each conducted alone or in conjunction with other procedures; this will depend on the research question, which in turn will determine the study design. Some examples of study designs that are compatible with these protocols are: (1) time series studies, which aim to describe longitudinal changes in performance; (2) quantification of individual variability, which aims to determine the reliability of the measures; (3) cross-sectional corr...

Watch this Scientific Journal Video about Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats at JoVE.com

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats

We present three protocols that assess different forms of impulsivity in rats and other small mammals. Intertemporal choice procedures evaluate the tendency to discount the value of delayed outcomes. Differential reinforcement of low rates and feature-negative discrimination evaluate response inhibition capacity with and without punishment for inappropriate responses, respectively.

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is ...

Research

JoVE Journal

Behavior

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

Systematic Assessment of Well-Being in Mice for Procedures Using General Anesthesia

In keeping with the 3R Principle (Replacement, Reduction, Refinement) developed by Russel and Burch, scientific research should use alternatives to animal ...

Noninvasive, In-pen Approach Test for Laboratory-housed Pigs

Traumatic brain injury (TBI) incidences have increased in both civilian and military populations, and many researchers are adopting a porcine model for ...

A Laboratory Method to Measure Contagious Yawning in Rats

Communication is an essential aspect of animal social life. Animals may influence one another and come together in schools, flocks, and herds. ...

Assessing the Autonomic and Behavioral Effects of Passive Motion in Rats using Elevator Vertical Motion and Ferris-Wheel Rotation

The overall goal of this study is to assess the autonomic and behavioral effects of passive motion in rodents using the elevator vertical motion and ...