Name: a method for evaluating the reinforcing properties of ethanol in rats without water deprivation, saccharin fading or extended access training
Uploaded: 2017-01-29T13:00:00
Description: Watch this Scientific Journal Video about A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training at JoVE.com

This work was supported by the Swedish Research Council.

All procedures are conducted in accordance with the NIH Guide for Care and Use of Laboratory Animals.
1. Animal Care and Housing
<ol>
	<li>Upon arrival in the colony, house male Wistar rats weighing 200 - 225 g at arrival in pairs in a temperature (21 &#176;C) and humidity-controlled environment with a reversed 12 h light-dark cycle. 
	Note: Depending on the rationale of the experiments, rats may be single-housed.</li>
	<li>Allow the rats to acclimate to the vivarium and the light cycle for at least one wee...

<ol>
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A., Weiss, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Suppression+of+ethanol-reinforced+behavior+by+naltrexone+is+associated+with+attenuation+of+the+ethanol-induced+increase+in+dialysate+dopamine+levels+in+the+nucleus+accumbens.">Suppression of ethanol-reinforced behavior by naltrexone is associated with attenuation of the ethanol-induced increase in dialysate dopamine levels in the nucleus accumbens.</a> The Journal of neuroscience : the official journal of the Society for Neuroscience. 18, 10663-10671 (1998).</li><li>Biggs, T. A., Myers, R. 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With this protocol, we are presenting a new method to acquire and maintain stable oral self-administration of 20% ethanol in rats that, contrary to classic models of ethanol self-administration, does not require the use of water deprivation, extended access training, or saccharin/sucrose fading12. Furthermore, naltrexone, a currently FDA-approved medication for alcohol dependence, successfully decreases alcohol self-administration and the motivation to consume alcohol of Wistar rats trained with this protocol....

The development of animal models to study the reinforcing effects of drugs has proven an important tool to study human drug addiction. More specifically, operant self-administration is a widely used behavioral model that is one of the most effective means for assessing the positive reinforcing effects of an orally consumed ethanol solution. An early issue with developing such a model was the primary aversive taste of high concentrations of ethanol for most rodents, a phenomenon that is also shared in humans with little or no experience with alcohol1. A standard protocol to overcome this barrier requires water deprivation and/or saccharin or sucrose fading for the acquisition and maintenance of self-administration. However, these two approaches are not advantageous. They require long periods of training to simply initiate responding for ethanol and obtain a relative success rate of acquisition. The use of sweeteners also introduces a potential bias in the interpretation of the self-administration data. These limitations don&#39;t apply to the following protocol.
Briefly, Samson and colleagues2 have shown that dissolving ethanol in a sweet solution of 20% sucrose and then fading out the sweetness over 4 weeks of training is required to initiate responding for 10% ethanol in water. Furthermore, reliable ethanol intake is usually achieved in 6 to 8 weeks1-3. This approach is highly problematic. First, it requires extended periods of training before investigators can begin to measure ethanol self-administration. In contrast, intravenous self-administration of cocaine or heroin requires 0 - 1 days of pre-drug training on a food-delivering lever in food restricted animals, and stable responding for drug is often achieved in 10 - 12 days4,5. Another limitation of this method is the fact that saccharin and sucrose are highly rewarding to rats and elicit brain activation patterns similar to drugs of abuse, thus introducing the potential for confounds in ethanol self-administration studies6-9. Finally, rats acquiring self-administration of an ethanol solution using this method show variability in acquisition and response rate1,10, with a substantial proportion of rats consistently excluded from experiments due to unsuccessful acquisition and/or insufficient response rate.
By contrast, with this protocol, we present a simple yet efficient method for acquisition and maintenance of oral self-administration of a 20% ethanol in water solution that does not necessitate water deprivation, sucrose/saccharin fading or extended access training. A recent investigation found that self-administration for oral ethanol displays an inverted U shaped dose response curve with highest ethanol intake during self-administration at a 20% ethanol concentration, thus providing a rationale for selecting 20% ethanol solution in our experimental design11.

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a method for evaluating the reinforcing properties of ethanol in rats without water deprivation, saccharin fading or extended access training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

Figure 1 shows the representative self-administration behavior of operant- and drug-naive Wistar rats (eight different cohorts amounting to a total of 239 rats) trained on a FR1 schedule to self-administer 20% ethanol without water deprivation or saccharin/sucrose fading during 30-minute sessions. With this protocol, rats initiate lever pressing to obtain an ethanol reward very quickly, already obtaining more than 10 rewards during the first sessions (Figure 1A</s...

Watch this Scientific Journal Video about A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training at JoVE.com

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

The overall goal of this protocol is to quickly initiate operant responding for alcohol in rats with a method that is convenient for experiementers and, contrary to standard methods, does not require water deprivation, or saccharin sucrose fading. So this method is a very useful tool to answer key questions about the neurobiology and neuropharmacology of alcohol reward in alcohol seeking in rats. The main advantage of this technique is that it does not require saccharin sucrose fading to initiate alcohol responding in rats.First eliminating the potentially downfall of using sweeteners in ethanol self-administration administration procedure. For this experiment, obtain rats weighing 200 to 225 grams. Wistar males are used here.House them in pairs or singly, depending on the rationale of the experiment. Keep the colony on a reverse 12-12 light-dark cycle with controlled temperature and humidity and conduct the experiments during the dark phase. Weigh the animals weekly, and permit them to acclimate for at least one week before beginning the experiment.Do not limit the rat's access to food and water. It isn't necessary for conditioning. Conduct all the behavior training in the same sized operant chamber with a flood grid and waste pan.The chamber must be fitted to a vented, sound-attenuating cubicle. Each chamber must have stimulus lights, syringe pumps, and two retractable levers. The levels should be positioned laterally to a liquid cup receptacle.Each chamber should be under automated control with a computer interface. Use this software to prepare the operant conditioning program as needed. For example, execute the following commands.Extend two levers to mark the onset of the session and to signal availability of alcohol. Have the ethanol lever, when pressed, deliver 100 microliters of 20%ethanol into the adjacent drinking well, and time-out for five seconds. Signal the time-out by illuminating a cue light above the lever.The other lever, when pressed, has no programmed consequence, and serves as a control for non-specific behavior. Even during time-outs, record how the rats use the levers, although there is no consequence to the rat. After 30 minutes, retract the two levers to signal the end of the session.Load an ethanol solution, made from 95%ethanol and tap water, into a syringe. Eject the solution without introducing air bubbles into the tap lines. Manually confirm the solution's flow.Always manually test the devices. Also, always dry out the solution receptacle before starting any session. Prior to beginning a session, load the software controls and make certain everything is operational.Move the rats to the testing room in a transport cage, and assign one rat to each chamber. Keep the testing room at the same temperature and humidity as the vivarium. Load the rats into their chambers in a consistent manner, and at the same time of day for each session.Then start the software to initiate the session. After the session ends, return the rats to the vivarium and use a disinfectant to clean the operant conditioning cages. Conduct the sessions daily, five to six times per week.After each session, calculate the mean number of active lever presses, inactive lever presses, and alcohol rewards. Performance will have stabilized when over three consecutive sessions the rewards do not vary by more than 15%Rats on a stable baseline can then be manipulated. One possible manipulation for rats on the stabilized baseline is to assess their motivation for the ethanol rewards.To do that, subject them to a progressive ratio schedule. Program the chambers to initially deliver a single volume of alcohol with one lever press, but increase the number of lever presses required after each alcohol reinforcer. Each animal will reach a break point, corresponding to the number of presses made for the last reinforcer earned.This model has been evaluated for its predictive validity using the approved alcoholics medication, naltrexone. Indeed, predictive validity was established, and therefore the model can be used to evaluate new drug candidates. Initially, inject the rats with saline 30 minutes prior to each session to habituate them to the injection.Analyze the results of the sessions and proceed when the number of rewards between the last two sessions varies by 15%or less. Then, deliver the naltrexone in saline with pH adjusted to neutral. Randomize the testing order between the different treatment groups, and untreated controls.Between drug administrations, let each rat go through two normal sessions with no treatment, exposed only to saline. This functions as the washout period, and resets the rat. Repeat the tests until ultimately each conditioned rat receives each treatment level once, and the control treatment once.After analyzing the data, the most effective dose can be selected to use on the animals during progressive ratio testing. Using the described protocol, 239 rats from eight different cohorts were trained to self-administer the alcohol reward without water deprivation or saccharin sucrose fading. Rats initiated lever pressing quickly, obtaining more than 10 rewards in the first session.Eventually, the rats obtained stable responding rates, earning about 24 rewards over each half hour session. An FDA approved drug, naltrexone, was tested at three concentrations. As expected, naltrexone treatment produced a dose-dependent decrease in alcohol self-administration, providing an important pharmacological validation for this protocol.Also as expected, naltrexone reduced the rat's motivation for alcohol under a progressive ratio schedule, as shown by the decline in the break point measure. After watching this video, you should have a good understanding on how to quickly initiate ethanol operant responding in rats without using water deprivation or saccharin sucrose fading procedure. With this protocol, rats acquire stable self-administration rates in about two weeks, that result in pharmacologically relevant blood alcohol concentrations.While attempting this procedure, it is important to keep the day-to-day condition as consistent as possible. It is also critical that the ethanol is correctly delivered into the receptacle from the first reinforced response, as any malfunction may alter or delay acquisition of ethanol self-administration. Following this procedure, other experiments can be carried out to study the neural basis of alcohol seeking and taking.

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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 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 ...

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.

Detailed instructions are provided on how to train rats to voluntarily dive underwater through a 5 m long Plexiglas maze. Because the brains of rats have been very well characterized, voluntarily diving rats may help elucidate the central pathways of the mammalian diving response.

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

A Treatment Package without Escape Extinction to Address Food Selectivity

Feeding difficulties and feeding disorders are a commonly occurring problem for young children, particularly children with developmental delays including autism. Behavior analytic interventions for the treatment of feeding difficulties oftentimes include escape extinction as a primary component of treatment. The use of escape extinction, while effective, may be problematic as it is also associated with the emergence of challenging behavior (e.g., extinction burst). Such challenging behavior may be an acceptable side effect in treatment cases where feeding problems are severe and chronic (e.g., failure to thrive). However, in more acute cases (e.g., selective eating), the negative side effect may be unwarranted and undesired. More recent research on the behavioral treatment of food selectivity has begun to evaluate treatments for feeding difficulties that do not include escape extinction (e.g., demand fading, behavioral momentum), with some success. However, research to date reveals individual differences in responsiveness to such treatments and no clear preferable treatment has emerged. This manuscript describes a multi-component treatment package that includes shaping, sequential presentation and simultaneous presentation, for the treatment of food selectivity in four young children with developmental delays. This treatment package extends the literature on the behavioral treatment for food selectivity and offers a multi-component treatment protocol that may be clinically applicable across a range of treatment scenarios and settings.

Feeding difficulties are a common problem for children with developmental disorders, including autism, and behavioral interventions often include escape extinction. Recent research has begun to evaluate treatments that do not include escape extinction. This manuscript describes a multicomponent treatment package that does not use escape extinction to treat feeding difficulties.

Feeding difficulties and feeding disorders are a commonly occurring problem for young children, particularly children with developmental delays including ...

Pavlovian Conditioned Approach Training in Rats

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience, or the transformation of neutral stimuli into attractive, &#34;wanted&#39; stimuli capable of motivating behavior. Pavlovian conditioned approach (PCA) develops after the response-independent presentation of a conditioned stimulus (CS; e.g., a lever) that predicts the delivery of an unconditioned stimulus (US; e.g., a food pellet) and can be used to measure incentive salience. During training, three patterns of conditioned responses (CRs) can develop: sign-tracking behavior (CS-directed CR), goal-tracking behavior (US-directed CR), and an intermediate response (both CRs). Sign-trackers attribute incentive salience to reward-related cues and are more vulnerable to cue-induced reinstatement of drug-seeking as well as other addiction-related behaviors, making PCA a potentially valuable procedure for studying addiction vulnerability. Here, we describe materials and methods used to elicit PCA behavior from rats as well as analyze and interpret PCA behavior in individual experiments.

Here, we present a protocol to elicit Pavlovian conditioned approach behavior in rats. This procedure can be used to measure individual differences in the tendency to approach and attribute incentive salience to reward-related cues and investigate addiction vulnerability.

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the ...

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 ...

A New Method for Inducing a Depression-Like Behavior in Rats

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression.
Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with na&#239;ve rats from the contagion group (1 na&#239;ve rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and na&#239;ve rats.
This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test.
A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, na&#239;ve rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

This protocol describes a new model by which healthy rats could contract depression over a given time periodthrough contagion by exposure to chronic unpredictable stressed (CUS) rats.

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is ...