The Effect of Personality Traits on Cognitive Behavioral Therapy Outcomes in Student Pharmacists with Rat Phobia: A Randomized Clinical Trial.

Background: Little is known about which personality traits determine the effectiveness of various types of cognitive-behavioral therapy (CBT) on animal phobia. The objective of the present study was to investigate a possible association between personality traits and the outcome of single- and multi-session CBT. Methods: The present randomized clinical trial was conducted from November 2018 to May 2019 in Shiraz, Iran. Forty female students with rat phobia, who met the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria, were systematically allocated into a single- and a multi-session therapy group (odd numbers one-session treatment, even numbers multi-session treatment). In both groups, the students were gradually exposed to rats as part of the treatment. Psychological measures (state-anxiety, rat phobia, and disgust questionnaires) were used to compare pre- and post-intervention outcomes. Multivariate analysis of covariance was used to assess which personality traits influenced the intervention outcome. The statistical analysis was performed using SPSS (version 20.0) and P values<0.05 were considered statistically significant. Results: Rat phobia was positively and significantly affected by conscientiousness (P=0.001) and agreeableness (P=0.003). Of these personality traits, only a higher degree of conscientiousness resulted in a further reduction of state anxiety after the intervention (P=0.005). There were no significant differences between the pre- and post-intervention outcomes. Conclusion: The outcome of single- and multi-session rat phobia therapies was associated with specific personality traits of the participants, namely conscientiousness and agreeableness. Both intervention methods had an equal effect on reducing rat phobia.

Rigor and reproducibility in rodent behavioral research.

Behavioral neuroscience research incorporates the identical high level of meticulous methodologies and exacting attention to detail as all other scientific disciplines. To achieve maximal rigor and reproducibility of findings, well-trained investigators employ a variety of established best practices. Here we explicate some of the requirements for rigorous experimental design and accurate data analysis in conducting mouse and rat behavioral tests. Novel object recognition is used as an example of a cognitive assay which has been conducted successfully with a range of methods, all based on common principles of appropriate procedures, controls, and statistics. Directors of Rodent Core facilities within Intellectual and Developmental Disabilities Research Centers contribute key aspects of their own novel object recognition protocols, offering insights into essential similarities and less-critical differences. Literature cited in this review article will lead the interested reader to source papers that provide step-by-step protocols which illustrate optimized methods for many standard rodent behavioral assays. Adhering to best practices in behavioral neuroscience will enhance the value of animal models for the multiple goals of understanding biological mechanisms, evaluating consequences of genetic mutations, and discovering efficacious therapeutics.

"They're always there": resident experiences of living with rats in a disadvantaged urban neighbourhood.

BACKGROUND: The presence of urban rats in the neighbourhood environment may negatively impact the physical and mental health of residents. Our study sought to describe the experiences with, perceptions of, and feelings towards rats and rat control efforts among a group of disadvantaged urban residents in Vancouver, Canada. METHODS: Semi-structured interviews were held with 20 members of the Vancouver Area Network of Drug Users (VANDU) recruited by VANDU staff. Interviews were audio recorded, transcribed, and analyzed using thematic analysis. RESULTS: Participants reported daily sightings of rats and close contact during encounters. Participants generally disliked encountering rats, raising issues of health and safety for themselves and the community due to the belief that rats carry disease. Fear of rats was common, and in some cases resulted in avoidance of rats. Effects of rats on participants were particularly pronounced for those living with rats in the home or for homeless participants who described impacts on sleep due to the sounds made by rats. Although rats were viewed as more problematic in their neighbourhood than elsewhere in Vancouver, participants believed there to be a lack of neighbourhood-level control initiatives that angered and disheartened participants. In combination with other community-level concerns (e.g., housing quality and availability), the presence of rats was viewed by some to align with a general disregard for the community and its residents. CONCLUSIONS: This study suggests that the presence of rats in urban centres may have several consequences on the physical and mental health of residents living in close contact with them. These effects may be exacerbated with continued contact with rats and when residents perceive a lack of initiative to control rats in their neighbourhood. As such, research and policies aimed at mitigating the health risks posed by rats should extend beyond disease-related risk and incorporate diverse health outcomes.

Relatedness decreases and reciprocity increases cooperation in Norway rats.

Kin selection and reciprocity are two mechanisms underlying the evolution of cooperation, but the relative importance of kinship and reciprocity for decisions to cooperate are yet unclear for most cases of cooperation. Here, we experimentally tested the relative importance of relatedness and received cooperation for decisions to help a conspecific in wild-type Norway rats (Rattus norvegicus). Test rats provided more food to non-kin than to siblings, and they generally donated more food to previously helpful social partners than to those that had refused help. The rats thus applied reciprocal cooperation rules irrespective of relatedness, highlighting the importance of reciprocal help for cooperative interactions among both related and unrelated conspecifics.

Where is the TMT? GC-MS analyses of fox feces and behavioral responses of rats to fear-inducing odors.

TMT (2,5-dihydro-2,4,5-trimethylthiazoline) is known as a component of fox feces inducing fear in rodents. However, no recent chemical analyses of fox feces are available, and few studies make direct comparisons between TMT and fox feces. Fox feces from 3 individuals were used to prepare 24 samples to be analyzed for the presence of TMT using gas chromatography-mass spectrometry (GC-MS). When TMT was added in low amounts (50-2000 nmol/g), TMT was detected in 10 out of 11 samples. When no TMT was added, TMT was detected in only 1 out of 13 samples. In a second experiment, we tested the behavioral response of male Brown Norway (BN) and Wistar rats to either fox feces, a low amount of TMT (0.6 nmol) or 1-hexanol. TMT induced freezing in the rats, but fox feces induced significantly more freezing episodes and longer total duration of freezing in both rat strains. In experiment 3, male BN rats were exposed over several days to fox feces, rat feces, 1-hexanol, cadaverine, 2-phenylethylamine, and TMT, one odor at a time. Fox feces induced significantly more freezing episodes of a longer total duration than any of the other odors, with rat feces and 1-hexanol giving rise to the lowest amount of freezing. This finding, together with our inability to verify the presence of TMT in fox feces, indicates that the concentration of TMT in our fox feces samples was below 50 nmol/g. It may also be that other compounds in fox feces play a role in its fear-inducing properties.

Treating Generational Stress: Effect of Paternal Stress on Development of Memory and Extinction in Offspring Is Reversed by Probiotic Treatment.

Early-life adversity is a potent risk factor for mental-health disorders in exposed individuals, and effects of adversity are exhibited across generations. Such adversities are also associated with poor gastrointestinal outcomes. In addition, emerging evidence suggests that microbiota-gut-brain interactions may mediate the effects of early-life stress on psychological dysfunction. In the present study, we administered an early-life stressor (i.e., maternal separation) to infant male rats, and we investigated the effects of this stressor on conditioned aversive reactions in the rats' subsequent infant male offspring. We demonstrated, for the first time, longer-lasting aversive associations and greater relapse after extinction in the offspring (F1 generation) of rats exposed to maternal separation (F0 generation), compared with the offspring of rats not exposed to maternal separation. These generational effects were reversed by probiotic supplementation, which was effective as both an active treatment when administered to infant F1 rats and as a prophylactic when administered to F0 fathers before conception (i.e., in fathers' infancy). These findings have high clinical relevance in the identification of early-emerging putative risk phenotypes across generations and of potential therapies to ameliorate such generational effects.

Assessment of Itch and Pain in Animal Models and Human Subjects.

For the past century, scientists have developed a variety of methods to evaluate itch and pain in both animal models and human subjects to throw light on some of the most important pathways mediating these unpleasant sensations. Discoveries in the mechanisms underlying itch and pain in both physiological and pathological conditions relied greatly upon these studies and may eventually lead to the discovery of new therapeutics. However, it was a much more complicated job to access itch and pain in animal models than in human subjects due to the subjective nature of these sensations. The results could be contradictory or even misleading when applying different methodologies in animal models, especially under pathological conditions with a mixed sensation of itch and pain. This chapter introduces and evaluates some of the classical and newly designed methodologies to access the sensation of itch and pain in animal models as well as human subjects.

"Shall two walk together except they be agreed?" Spatial behavior in rat dyads.

When animals explore an unfamiliar environment, they gather information that enables them to form a cognitive representation of that environment and to use it subsequently in traveling there. In the present study, rats were tested in a large arena as singles, then in dyads, and finally, again as singles, in order to examine the effect of the social environment on exploration. Traveling in dyads facilitated exploration compared to the behavior of the same rats when they explored alone. Specifically, each rat in a dyad traveled a greater distance with higher velocity and took wider turns compared to its lone traveling. Moreover, rats in dyads spent a long time together, shared a home base, and when traveling in the same direction, one rat was leading the other. In addition to exploring the same locations, leaders explored more "private" locations, not visited by the other rat. Features of the dyad behavior were carried over to the behavior of the same rats when tested as individuals, after the dyad trial. Compared to singles, dyads represent the first step toward grouping, and it is suggested that the conspicuous change between the behavior of a rat as single compared to its behavior when in a dyad should be greater than any further changes that may occur in spatial cognitive behavior of triads, quartets, or larger groups. In other words, while the present changes in spatial cognition observed in dyads represent a small step toward grouping, they are a giant leap for the individual.

Effects of neonatal fluoxetine exposure on behavior across development in rats selectively bred for an infantile affective trait.

Infants born to women with depressive symptoms are at higher risk for insecure attachment and behavioral problems. Thus current medical practice is to continue psychotropic medication of pregnant women with depression despite concerns about its behavioral teratology. There are few animal studies focused on long-term behavioral effects of prenatal antidepressant exposure; in addition, studies have not looked at individual differences in baseline affective state as a source of response variability. In this study, fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was administered to male and female rat pups from postnatal days 2-7 to model exposure to antidepressants in the human third trimester. Four behavioral measures were conducted from the neonatal to adult age periods in Low and High lines selectively bred for their rate of ultrasonic vocalizations after brief maternal separation. Neonatal fluoxetine administration decreased distress calls in both lines, but to a greater extent in High line rats than Low line. Neonatal fluoxetine also impaired motor coordination in neonates. Neonatal fluoxetine administration decreased social behavior in both juvenile and adult subjects. Fluoxetine-related reductions in anxiety behavior were not observed at the two older ages. As expected, High line subjects displayed more anxiety behavior than Low line subjects at all three test ages. These results suggest that there are may be significant behavioral consequences of antidepressant use during late pregnancy on offspring maternal attachment and social behavior, with implications for increased risk of autism spectrum disorders.

The visual cliff's forgotten menagerie: rats, goats, babies, and myth-making in the history of psychology.

Eleanor Gibson and Richard Walk's famous visual cliff experiment is one of psychology's classic studies, included in most introductory textbooks. Yet the famous version which centers on babies is actually a simplification, the result of disciplinary myth-making. In fact the visual cliff's first subjects were rats, and a wide range of animals were tested on the cliff, including chicks, turtles, lambs, kid goats, pigs, kittens, dogs, and monkeys. The visual cliff experiment was more accurately a series of experiments, employing varying methods and a changing apparatus, modified to test different species. This paper focuses on the initial, nonhuman subjects of the visual cliff, resituating the study in its original experimental logic, connecting it to the history of comparative psychology, Gibson's interest in comparative psychology, as well as gender-based discrimination. Recovering the visual cliff's forgotten menagerie helps to counter the romanticization of experimentation by focusing on the role of extrascientific factors, chance, complexity, and uncertainty in the experimental process.

Retrieval-induced forgetting in rats.

"Retrieval-induced forgetting" in rats was evaluated using a modified spontaneous object recognition test. The test consisted of a sample phase, retrieval or interference phase, and a test phase with 60-min delay period inserted between the phases. Rats were randomly assigned to one of three groups (control, retrieval and interference) and allowed to explore the field in which two different objects (A, B) were placed in the sample phase. In the retrieval phase, two identical objects (B, B), which were the same as one of the objects presented in the sample phase, were placed again. In the interference phase, two identical objects (C, C), which were novel for animals, were placed. In the test phase, two different objects (A, D), one of which was identical to that presented in sample phase (familiar object) and the other was novel, were placed and the time spent exploring each object was analyzed. While the exploration of the novel object was significantly longer than that of the familiar object in rats subjected to the interference phase, rats subjected to the retrieval phase could not discriminate between the familiar and the novel objects at the test phase. These results demonstrate the "retrieval-induced forgetting" phenomenon in a spontaneous object recognition test in rats.

Behavioral analysis in laboratory rats: Challenges and usefulness of 50-kHz ultrasonic vocalizations.

Many rodent species emit and detect vocalizations in the ultrasonic range. Rats use three classes of ultrasonic vocalizations depending on developmental stage, experience and the behavioral situation. Calls from one class emitted by juvenile and adult rats, the so-called 50-kHz calls, are typical for appetitive and social situations. This review provides a brief historical account on the introduction of 50-kHz calls in behavioral research followed by a survey of their scientific applications focusing on the last five years, where 50-kHz publications reached a climax. Then, specific methodological challenges will be addressed, like how to measure and report 50-kHz USV, the problem of assignment of acoustic signals to a specific sender in a social situation, and individual variability in call propensity. Finally, the intricacy of interpreting 50-kHz results will be discussed focusing on the most prevalent ones, namely as communicative signals and/or readouts of the sender's emotional status.

Acquired equivalence of cues by presentation in a common context in rats.

It is well established that humans and other animals may treat two perceptually different cues alike, if the cues have been individually paired with a common antecedent or a common consequence. Recently, Molet et al. (Psychon Bull Rev 18:618-623, 2011) reported evidence for a new form of acquired equivalence in human conditional discrimination, namely context-mediated equivalence. In the present research, using a flavor conditioning procedure, we asked whether rats would show similar context-mediated equivalence to demonstrate that this new form of acquired equivalence is a general phenomenon. Rats experienced two flavor cues A and B each presented either in the same context, X, or each in its own distinctive context, X or Y. Subsequently, the rats experienced B with sucrose in a third context, Z, and then the generalization of conditioning to A was assessed. When tested in Context Z, consumption of A was more marked when A and B had both been presented in the same context than when they had been presented in two different contexts. Thus, importantly, in the absence of the training context, cues that shared a common context at different times came to be treated as equivalent. This represents the first evidence of context-mediated equivalence in a nonhuman species.

"Play it Again": a new method for testing metacognition in animals.

Putative metacognition data in animals may be explained by non-metacognition models (e.g., stimulus generalization). The primary objective of the present study was to develop a new method for testing metacognition in animals that may yield data that can be explained by metacognition but not by non-metacognition models. Next, we used the new method with rats. Rats were first presented with a brief noise duration which they would subsequently classify as short or long. Rats were sometimes forced to take an immediate duration test, forced to repeat the same duration, or had the choice to take the test or repeat the duration. Metacognition, but not an alternative non-metacognition model, predicts that accuracy on difficult durations is higher when subjects are forced to repeat the stimulus compared to trials in which the subject chose to repeat the stimulus, a pattern observed in our data. Simulation of a non-metacognition model suggests that this part of the data from rats is consistent with metacognition, but other aspects of the data are not consistent with metacognition. The current results call into question previous findings suggesting that rats have metacognitive abilities. Although a mixed pattern of data does not support metacognition in rats, we believe the introduction of the method may be valuable for testing with other species to help evaluate the comparative case for metacognition.

Rats build and update topological representations through exploration.

Although rats are able to build complex spatial representations of their surroundings during exploration, the nature of the encoded information is still a matter for debate. In particular, it is not well established if rats can process the topological structure of the environment in such a way that they are aware of the connections existing between remote places. Here, rats were first exposed for four 5-min trials to a complex environment divided into several sectors that were separated by doors allowing either unrestricted or restricted access to other sectors. In the fifth test trial, we measured the behavior of the animals while they explored the same environment in which, however, they faced changes that either altered or did not alter the topological structure of the environment. In experiment 1, closing previously opened doors prevented the rat from having direct access between corresponding sectors. In experiment 2, opening previously closed doors allowed direct access between sectors that had not been directly accessible. In each experiment, control doors allowed us to discard the mere influence of door manipulation. We compared the rats' exploratory behavior in response to door manipulations that either strongly altered or did not alter the ability to commute between sectors and found evidence that the animals displayed differential reactions to the two types of door manipulations. This implies that during exploration rats build a precise map of the connectivity of space that can be flexibly updated and used for efficient navigation.

Rats distinguish between absence of events and lack of evidence in contingency learning.

The goal of three experiments was to study whether rats are aware of the difference between absence of events and lack of evidence. We used a Pavlovian extinction paradigm in which lights consistently signaling sucrose were suddenly paired with the absence of sucrose. The crucial manipulation involved the absent outcomes in the extinction phase. Whereas in the Cover conditions, access to the drinking receptacle was blocked by a metal plate, in the No Cover conditions, the drinking receptacle was accessible. The Test phase showed that in the Cover conditions, the measured expectancies of sucrose were clearly at a higher level than in the No Cover conditions. We compare two competing theories potentially explaining the findings. A cognitive theory interprets the observed effect as evidence that the rats were able to understand that the cover blocked informational access to the outcome information, and therefore the changed learning input did not necessarily signify a change of the underlying contingency in the world. An alternative associationist account, renewal theory, might instead explain the relative sparing of extinction in the Cover condition as a consequence of context change. We discuss the merits of both theories as accounts of our data and conclude that the cognitive explanation is in this case preferred.

Changing within-trial array location and target object position enhances rats' (Rattus norvegicus) missing object recognition accuracy.

Six rats were trained to find a previously missing target or 'jackpot' object in a square array of four identical or different objects (the test segment of a trial) after first visiting and collecting sunflower seeds from under the other three objects (the study segment of a trial). During training, objects' local positions within the array and their global positions within the larger foraging array were varied over trials but were not changed between segments within a trial. Following this training, rats were tested on their accuracy for finding the target object when a trial's test array was sometimes moved to a different location in the foraging arena or when the position of the target object within the test array had been changed. Either of these manipulations initially slightly reduced rats' accuracy for finding the missing object but then enhanced it. Relocating test arrays of identical objects enhanced rats' performance only after 10-min inter-segment intervals (ISIs). Relocating test arrays of different objects enhanced rats' performance only after 2-min ISIs. Rats also improved their performance when they encountered the target object in a new position in test arrays of different objects. This enhancement effect occurred after either 2- or 30-min ISIs. These findings suggest that rats separately retrieved a missing (target) object's spatial and non-spatial information when they were relevant but not when they were irrelevant in a trial. The enhancement effects provide evidence for rats' limited retrieval capacity in their visuo-spatial working memory.

Prospective memory in the rat.

The content of prospective memory is comprised of representations of an action to perform in the future. When people form prospective memories, they temporarily put the memory representation in an inactive state while engaging in other activities, and then activate the representation in the future. Ultimately, successful activation of the memory representation yields an action at an appropriate, but temporally distant, time. A hallmark of prospective memory is that activation of the memory representation has a deleterious effect on current ongoing activity. Recent evidence suggests that scrub jays and non-human primates, but not other species, are capable of future planning. We hypothesized that prospective memory produces a selective deficit in performance at the time when rats access a memory representation but not when the memory representation is inactive. Rats were trained in a temporal bisection task (90 min/day). Immediately after the bisection task, half of the rats received an 8-g meal (meal group) and the other rats received no additional food (no-meal group). Sensitivity to time in the bisection task was reduced as the 90-min interval elapsed for the meal group but not for the no-meal group. This time-based prospective-memory effect was not based on response competition, an attentional limit, anticipatory contrast, or fatigue. Our results suggest that rats form prospective memories, which produces a negative side effect on ongoing activity.

Route selection by rats and humans in a navigational traveling salesman problem.

Spatial cognition is typically examined in non-human animals from the perspective of learning and memory. For this reason, spatial tasks are often constrained by the time necessary for training or the capacity of the animal's short-term memory. A spatial task with limited learning and memory demands could allow for more efficient study of some aspects of spatial cognition. The traveling salesman problem (TSP), used to study human visuospatial problem solving, is a simple task with modifiable learning and memory requirements. In the current study, humans and rats were characterized in a navigational version of the TSP. Subjects visited each of 10 baited targets in any sequence from a set starting location. Unlike similar experiments, the roles of learning and memory were purposely minimized; all targets were perceptually available, no distracters were used, and each configuration was tested only once. The task yielded a variety of behavioral measures, including target revisits and omissions, route length, and frequency of transitions between each pair of targets. Both humans and rats consistently chose routes that were more efficient than chance, but less efficient than optimal, and generally less efficient than routes produced by the nearest-neighbor strategy. We conclude that the TSP is a useful and flexible task for the study of spatial cognition in human and non-human animals.

Responding in a test of decision-making under risk is under moderate genetic control in the rat.

BACKGROUND: Risk-taking, measured with laboratory tasks such as the Balloon Analog Risk Task (BART), is associated with real-life manifestations of risky behaviors, which may be an important component of inherited liability to alcohol use disorders. To identify genomic factors that influence these traits, the current study (i) characterized performance of a rodent version of the BART in multiple inbred rat strains, (ii) tested the degree to which performance was under genetic control, (iii) explored sex differences in performance, and (iv) evaluated the risk-taking behavior of F1 progeny of high-risk- and low-risk-taking strains to examine modes of inheritance. METHODS: Male and female rats (N = 100) from 5 inbred strains (Wistar-Furth, Fischer-344, Lewis, Spontaneously Hypertensive, Brown Norway) and Wistar-Furth × Fischer-344 hybrids were tested in the rat-BART, as well as in tests of locomotor activity, sucrose preference, and general motivation. RESULTS: About 55% of the variance in risk-taking behavior was attributable to heritable factors. The Fischer-344 strain was the most risk-taking and the most variable in responding. The mating of low-risk-taking Wistar-Furth and Fischer-344 rats produced progeny that behaved most like the Fischer-344 strain. Consistent with prior research in this laboratory (Jentsch et al., 2010), all rats were sensitive to changes in both risk and reinforcement parameters in the rat-BART; rats decreased voluntary risk-taking in the face of increasing risk and increased lever pressing when reinforcement probabilities were reduced. CONCLUSIONS: Our results endorse a moderately heritable pattern of risk-taking behavior in rats. The behavior of the hybrid progeny suggests a polygenic model with most gene effects transmitted by mode of dominant inheritance. The identification of high-risk and low-risk strains allows for isolation of quantitative trait loci associated with task performance and for probing the relationships between risk-taking and dimensions of alcohol use disorders.