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
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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>

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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 ...

Conducting behavioral procedures to assess impulsivity in rats provides insight into the environmental, neurophysiological, and neurochemical basis of impulsivity, that is, about the factors that trigger and underlie those behaviors. This protocol allow the study of impulsivity with a good balance of efficiency and accessibility, and instruction of data suitable for quantitative analysis. The performance in these protocols may be considered as an analog of impulsiveness in humans.Hence, human versions of them serve for the diagnosis and treatment of related psychiatric disorders such as ADHD or pathological gambling. Demonstrating the procedure with Patsy Moreno will be Gustavo Lago, a technician, and Pablo Saavedra, an undergraduate student from our laboratory. After beginning the food restriction regime, add 60 food pellets to the food receptacle to habituate food neophobia before introducing the rats to the conditioning chambers without the initiation of any protocol for 30 minutes to habituate the exploring responses.After the habituation stage, introduce the rats into the conditioning chambers for two additional daily 30-minute sessions of delivering a food pellet every 45 seconds to help the rats identify the source of the pellets. For intertemporal choice and differential reinforcement of low rates of responding, or DRL protocols, place one or two levers into the chamber and deliver food for every level press in conjunction with a free food pellet delivery every 45 seconds. For an intertemporal choice protocol, select the values for the delay and the magnitude of the reward.For example, choices for the larger-later, or LL alternative, deliver five food pellets after a 20-second fixed delay and choices for the small-sooner, or SS alternative, deliver one food pellet immediately. Select a finishing criterion, and end the sessions automatically after the completion of the specified criterion, for example, after 40 choice trials or after 50 minutes. Combine each alternative with a lever within the conditioning chamber, counterbalancing the laterality of the alternatives among the subjects, and make SS and LL alternatives available upon the accomplishment of a variable interval schedule.In free choice trials, when one of the levers is pressed after a certain interval has elapsed, the associated alternative will be activated. Both levers will be retracted, and the consequence associated with the SS or LL alternatives after the accomplishment of a variable interval schedule of reinforcement will be activated. After reward delivery, perform a time-out condition, adjusting the duration of this condition to equate the average duration of the intertrial intervals for both alternatives.The next choice trial begins after the completion of the time-out. If a subject selects one alternative for two consecutive trials, the program will determine that the next trial will be a forced trial of the remaining alternative, that is, in the next trial, both levers will be available, but only one will operate to ensure that the subject experiences the outcomes associated with both alternatives. For DRL programming, select the value of the minimum time after which responding will produce a reward.After the beginning of a session or after any lever-press response, start a countdown timer from the selected time value to zero. If the subject displays a response before the timer reaches the value of zero, the timer will reset so that the subject must wait for a new opportunity to obtain a reward. If subject emit a response after the timer reaches the value of zero, deliver a food pellet.The timer will be reset after two seconds to allow the animal to consume the pellet. For feature-negative discrimination, first select stimuli durations, intertrial interval durations, and finishing criteria for the sessions. After presenting a stimulus A in A-plus trials, deliver a food pellet.After presenting the same stimulus A accompanied by an additional stimulus X in AX-minus trials, do not deliver any food. After setting up the protocols in the computer software, clean the inner walls, ceiling, and grill floor of the operant chambers with an appropriate disinfectant solution to remove odors from the previous sessions or previous studies. Use the computer to manually activate and monitor the crucial inputs and outputs to make sure they work and check that the food dispenser holds enough food to be delivered during the session.Move the housing cages with the rats inside close to the conditioning chambers, and open the housing cage. Gently place eat rat in its corresponding conditioning chamber before closing the conditioning chambers in the isolating shells. Initiate the program and wait until the program is finished.If the data is not saved automatically, save the output files of the session in the computer drive or elsewhere. When the program is finished, gently return the rats to their corresponding housing cages and give complementary food to the animals according to the selected food restriction regime. In this intertemporal choice procedure, the log-ratio of the lever response rate associated with the SS alternative was higher in spontaneously hypertensive rats compared to wild-type rats, suggesting the ADHD model rats prefer an immediate reward at the expense of a richer but delayed alternative.In this representative DRL protocol experiment, the longitudinal data of a single rat with a 10-second temporal restraint on responding demonstrates that over time, the animal acquired experience in the task, eventually learning to respond around 10 seconds. This pharmacological experiment tested whether impulsive performance in a DRL procedure with a temporal restriction of 10 seconds was decreased with a treatment consisting of low levels of an antipsychotic drug. Blue density plots represent the distribution of responses when saline is administered, and salmon plots represent the distribution of such responses when haloperidol was administered.The upper embedded plots show response rates, and lower ones show reward rates for saline and haloperidol with the same color code as the former plots. It can be noted that the response rate was reduced for three to five subjects, specifically for those subjects with a high proportion of burst responses in the saline condition. Typically, in the feature-negative discrimination protocol, responding during the single stimulus plus food trials and during the compound stimulus without food trials do not differ substantially in early sessions.However, after a few sessions, the rats respond differentially in both types of trials, revealing that the addition of a second stimulus counteracts the response tendency controlled by the first. Importantly, the subjects exhibit quite robust individual differences in both types of trials. Take care that the appropriate protocols are loaded in the corresponding conditioning chambers, that the rats are correctly assigned to each chamber, and that all of the chambers are closed.After a baseline procedure has been completed, behavioral, pharmacological, or surgical treatments could be administered in order to test their effect on performance. The results are not always conclusive, so researchers might want to consider whether the observed data are dependent upon the selected parameters or are in fact induced by confounding factors. Be sure to handle the rats appropriately to avoid harming the rats and to avoid the rats harming you.

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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 abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

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 reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

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 drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

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 processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

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 human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

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

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

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 largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

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 experimentation whenever possible. When there is no alternative to animal experimentation, the total number of laboratory animals used should be the minimum needed to obtain valuable data. Moreover, appropriate refinement measures should be applied to minimize pain, suffering, and distress accompanying the experimental procedure. The categories used to classify the degree of pain, suffering, and distress are non-recovery, mild, moderate, or severe (EU Directive 2010/63). To determine which categories apply in individual cases, it is crucial to use scientifically sound tools.
The well-being-assessment protocol presented here is designed for procedures during which general anesthesia is used. The protocol focuses on home cage activity, the Mouse Grimace Scale, and luxury behaviors such as burrowing and nest building behavior as indicators of well-being. It also uses the free exploratory paradigm for trait anxiety-related behavior. Fecal corticosterone metabolites as indicators of acute stress are measured over the 24-h post-anesthetic period.
The protocol provides scientifically solid information on the well-being of mice following general anesthesia. Due to its simplicity, the protocol can easily be adapted and integrated in a planned study. Although it does not provide a scale to classify distress in categories according to the EU Directive 2010/63, it can help researchers estimate the degree of severity of a procedure using scientifically sound data. It provides a way to improve the assessment of well-being in a scientific, animal-centered manner.

We developed a protocol to assess well-being in mice during procedures using general anesthesia. A series of behavioral parameters indicating levels of well-being as well as glucocorticoid metabolites were analyzed. The protocol can serve as a general aid to estimate the degree of severity in a scientific, animal-centered manner.

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

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. Communication is also the way sexes interact during courtship and how rivals settle disputes without fighting. However, there are some behavioral patterns for which it is difficult to test the existence of a communicatory function, because several types of sensory modalities are likely involved. For example, contagious yawning is a communicatory act in mammals that potentially occurs through sight, hearing, smell, or a combination of these senses depending on whether the animals are familiar to one another. Therefore, to test hypotheses about the possible communicatory role of such behaviors, a suitable method is necessary to identify the participating sensory modalities.
The method proposed here aims to obtain yawn contagion curves for familiar and unfamiliar rats and evaluate the relative participation of visual and olfactory sensory modalities. The method uses inexpensive materials, and with some minor changes, it can also be used with other rodent species such as mice. Overall, the method involves the substitution of clear dividers (with or without holes) with opaque dividers (with or without holes) that either allow or prevent communication between rats placed in adjacent cages with holes in adjoining sides. Accordingly, four conditions can be tested: olfactory communication, visual communication, both visual and olfactory communication, and neither visual nor olfactory communication. As social interaction occurs between the rats, these test conditions simulate what may occur in a natural environment. In this respect, the method proposed here is more effective than traditional methods that rely on video presentations whose biological validity can raise concerns. Nonetheless, it does not discriminate between the potential role of hearing and roles of smell and vision in yawn contagion.

The method described here aims to obtain yawn contagion curves in pairs of familiar or unfamiliar male rats. Cages with holes separated by either clear or opaque partitions with (or without) holes are used to detect whether visual, olfactory, or both types of sensory cues can stimulate yawn contagion.

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 Ferris-wheel rotation devices. These assays can help confirm the integrity and normal functioning of the autonomic nervous system. They are coupled to quantitative measures based on defecation counting, open-field examination, and balance beam crossing. The advantages of these assays are their simplicity, reproducibility, and quantitative behavioral measures. The limitations of these assays are that the autonomic reactions could be epiphenomena of non-vestibular disorders and that a functioning vestibular system is required. Examination of disorders such as motion sickness will be greatly aided by the detailed procedures of these assays.

Protocols are presented to assess the autonomic and behavioral effects of passive motion in rodents 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 ...

Assessing the Coherence of Parents' Short Narratives Regarding their Child Using the Five-Minute Speech Sample Procedure

Valid and efficient measures for assessing the quality of parent-child relationships are needed to facilitate research and evidence-based practice with parents. This paper focuses on such a method, namely Five-Minute Speech Sample-Coherence (FMSS-Coherence). In this method, a parent is asked to speak for five uninterrupted minutes about her/his child and their relationship. The resulted narrative is coded for coherence, namely the extent to which the parent provides&#160;in the narrative&#160;a clear, consistent, multidimensional and well-supported portrayal of the child. FMSS-Coherence is based on attachment research that shows that the coherence of parents&#8217; narratives is indicative of the quality of the parent-child relationship and child adjustment. It overcomes the limitations of attachment narrative measures which are typically labor intensive. FMSS-Coherence is less nuanced than extant attachment narrative measures. Yet, studies of families from different cultural backgrounds, across different child ages and in the context of typically developing children as well as children with special needs suggest that coherence can be reliably evaluated using the FMSS procedure. Furthermore, parents&#8217; FMSS-Coherence is associated with parenting quality and children&#8217;s socio-emotional adjustment. Thus, it holds promise for researchers and practitioners who seek a relatively time- and cost-effective method for assessing the coherence of parents&#8217; narratives regarding their child.

Assessing the Coherence of Parents&#039; Short Narratives Regarding their Child Using the Five-Minute Speech Sample Procedure

This paper introduces a method for assessing the coherence of parents' short narratives regarding their child and their relationship using the five-minute speech sample procedure.

Valid and efficient measures for assessing the quality of parent-child relationships are needed to facilitate research and evidence-based practice with ...