Housing and Social Environments of African (Loxodonta africana) and Asian (Elephas maximus) Elephants in North American Zoos.

We evaluated 255 African (Loxodonta africana) and Asian (Elephas maximus) elephants living in 68 North American zoos over one year to quantify housing and social variables. All parameters were quantified for the both the day and the night and comparisons were made across these time periods as well as by species and sex. To assess housing, we evaluated not only total exhibit size, but also individual animals' experiences based on the time they spent in the unique environments into which the exhibits were subdivided. Variables developed to assess housing included measurements of area as a function of time (Total Space Experience), environment type (Indoor, Outdoor, In/Out Choice) and time spent on hard and soft flooring. Over the year, Total Space Experience values ranged from 1,273 square feet to 169,692 square feet, with Day values significantly greater than Night values (p<0.001). Elephants spent an average of 55.1% of their time outdoors, 28.9% indoors, and 16% in areas with a choice between being in or out. Time spent on hard flooring substrate ranged from 0% to 66.7%, with Night values significantly greater than Day (p<0.001). Social factors included number of animals functionally housed together (Social Experience) and social group characteristics such as time spent with juveniles and in mixed-sex groups. Overall Social Experience scores ranged from 1 to 11.2 and were significantly greater during the Day than at Night (p<0.001). There were few significant social or housing differences between African (N = 138) and Asian (N = 117) species or between males (N = 54) and females (N = 201). The most notable exception was Total Space Experience, with African and male elephants having larger Total Space Experience than Asian and female elephants, respectively (P-value<0.05). The housing and social variables evaluated herein have been used in a series of subsequent epidemiological analyses relating to various elephant welfare outcomes.

Determining Connections between the Daily Lives of Zoo Elephants and Their Welfare: An Epidemiological Approach.

Concerns about animal welfare increasingly shape people's views about the acceptability of keeping animals for food production, biomedical research, and in zoos. The field of animal welfare science has developed over the past 50 years as a method of investigating these concerns via research that assesses how living in human-controlled environments influences the behavior, health and affective states of animals. Initially, animal welfare research focused on animals in agricultural settings, but the field has expanded to zoos because good animal welfare is essential to zoos' mission of promoting connections between animals and visitors and raising awareness of conservation issues. A particular challenge for zoos is ensuring good animal welfare for long-lived, highly social species like elephants. Our main goal in conducting an epidemiological study of African (Loxodonta africana) and Asian (Elephas maximus) elephant welfare in 68 accredited North American zoos was to understand the prevalence of welfare indicators in the population and determine the aspects of an elephant's zoo environment, social life and management that are most important to prevent and reduce a variety of welfare problems. In this overview, we provide a summary of the findings of the nine papers in the collection titled: Epidemiological Investigations of North American Zoo Elephant Welfare with a focus on the life history, social, housing, and management factors found to be associated with particular aspects of elephant welfare, including the performance of abnormal behavior, foot and joint problems, recumbence, walking rates, and reproductive health issues. Social and management factors were found to be important for multiple indicators of welfare, while exhibit space was found to be less influential than expected. This body of work results from the largest prospective zoo-based animal welfare study conducted to date and sets in motion the process of using science-based welfare benchmarks to optimize care of zoo elephants.

Elephant Management in North American Zoos: Environmental Enrichment, Feeding, Exercise, and Training.

The management of African (Loxodonta africana) and Asian (Elephas maximus) elephants in zoos involves a range of practices including feeding, exercise, training, and environmental enrichment. These practices are necessary to meet the elephants' nutritional, healthcare, and husbandry needs. However, these practices are not standardized, resulting in likely variation among zoos as well as differences in the way they are applied to individual elephants within a zoo. To characterize elephant management in North America, we collected survey data from zoos accredited by the Association of Zoos and Aquariums, developed 26 variables, generated population level descriptive statistics, and analyzed them to identify differences attributable to sex and species. Sixty-seven zoos submitted surveys describing the management of 224 elephants and the training experiences of 227 elephants. Asian elephants spent more time managed (defined as interacting directly with staff) than Africans (mean time managed: Asians = 56.9%; Africans = 48.6%; p<0.001), and managed time increased by 20.2% for every year of age for both species. Enrichment, feeding, and exercise programs were evaluated using diversity indices, with mean scores across zoos in the midrange for these measures. There were an average of 7.2 feedings every 24-hour period, with only 1.2 occurring during the nighttime. Feeding schedules were predictable at 47.5% of zoos. We also calculated the relative use of rewarding and aversive techniques employed during training interactions. The population median was seven on a scale from one (representing only aversive stimuli) to nine (representing only rewarding stimuli). The results of our study provide essential information for understanding management variation that could be relevant to welfare. Furthermore, the variables we created have been used in subsequent elephant welfare analyses.

The Days and Nights of Zoo Elephants: Using Epidemiology to Better Understand Stereotypic Behavior of African Elephants (Loxodonta africana) and Asian Elephants (Elephas maximus) in North American Zoos.

Stereotypic behavior is an important indicator of compromised welfare. Zoo elephants are documented to perform stereotypic behavior, but the factors that contribute to performance have not been systematically assessed. We collected behavioral data on 89 elephants (47 African [Loxodonta africana], 42 Asian [Elephas maximus]) at 39 North American zoos during the summer and winter. Elephants were videoed for a median of 12 daytime hours per season. A subset of 32 elephants (19 African, 13 Asian) was also observed live for a median of 10.5 nighttime hours. Percentages of visible behavior scans were calculated from five minute instantaneous samples. Stereotypic behavior was the second most commonly performed behavior (after feeding), making up 15.5% of observations during the daytime and 24.8% at nighttime. Negative binomial regression models fitted with generalized estimating equations were used to determine which social, housing, management, life history, and demographic variables were associated with daytime and nighttime stereotypic behavior rates. Species was a significant risk factor in both models, with Asian elephants at greater risk (daytime: p<0.001, Risk Ratio = 4.087; nighttime: p<0.001, Risk Ratio = 8.015). For both species, spending time housed separately (p<0.001, Risk Ratio = 1.009), and having experienced inter-zoo transfers (p<0.001, Risk Ratio = 1.175), increased the risk of performing higher rates of stereotypy during the day, while spending more time with juvenile elephants (p<0.001, Risk Ratio = 0.985), and engaging with zoo staff reduced this risk (p = 0.018, Risk Ratio = 0.988). At night, spending more time in environments with both indoor and outdoor areas (p = 0.013, Risk Ratio = 0.987) and in larger social groups (p = 0.039, Risk Ratio = 0.752) corresponded with reduced risk of performing higher rates of stereotypy, while having experienced inter-zoo transfers (p = 0.033, Risk Ratio = 1.115) increased this risk. Overall, our results indicate that factors related to the social environment are most influential in predicting elephant stereotypic behavior rates.

Evaluation of Demographics and Social Life Events of Asian (Elephas maximus) and African Elephants (Loxodonta africana) in North American Zoos.

This study quantified social life events hypothesized to affect the welfare of zoo African and Asian elephants, focusing on animals that were part of a large multi-disciplinary, multi-institutional elephant welfare study in North America. Age was calculated based on recorded birth dates and an age-based account of life event data for each elephant was compiled. These event histories included facility transfers, births and deaths of offspring, and births and deaths of non-offspring herd mates. Each event was evaluated as a total number of events per elephant, lifetime rate of event exposure, and age at first event exposure. These were then compared across three categories: species (African vs. Asian); sex (male vs. female); and origin (imported vs. captive-born). Mean age distributions differed (p<0.05) between the categories: African elephants were 6 years younger than Asian elephants, males were 12 years younger than females, and captive-born elephants were 20 years younger than imported elephants. Overall, the number of transfers ranged from 0 to 10, with a 33% higher age-adjusted transfer rate for imported African than imported Asian elephants, and 37% lower rate for imported females than males (p<0.05). Other differences (p<0.05) included a 96% higher rate of offspring births for captive-born females than those imported from range countries, a 159% higher rate of birthing event exposures for captive-born males than for their imported counterparts, and Asian elephant females being 4 years younger than African females when they produced their first calf. In summarizing demographic and social life events of elephants in North American zoos, we found both qualitative and quantitative differences in the early lives of imported versus captive-born elephants that could have long-term welfare implications.

Incidence, Severity, and Welfare Implications of Lesions Observed Postmortem in Laying Hens from Commercial Noncage Farms in California and Iowa.

The egg industry is moving away from the use of conventional cages to enriched cage and noncage laying hen housing systems because of animal welfare concerns. In this study, the prevalence and severity of lesions in noncage laying hens from commercial farms in two of the largest egg-producing states, California and Iowa, were evaluated by postmortem examination. Hens that died or were culled were collected during early, mid, and late stages of the laying cycle from 16 houses on three farms. Of the 25 gross lesions identified for study, 22 were observed, with an average of four lesions per hen. Vent cannibalism, reduced feather cover, keel bone deformation, and beak abnormalities were the most frequent lesions, observed in ≥40% of hens. Other common lesions were cloacal prolapse (30.5%), footpad dermatitis (24.3%), and septicemia (23.1%). Beak abnormality and enteric disease had the highest proportion of severe lesions. Pearson chi-square analysis revealed a number of stage-of-lay effects (P ≤ 0.05), some of which differed by state. For both states combined, the lesions observed more frequently during early lay were beak abnormalities, northern fowl mite infestation, and cage layer fatigue, whereas during mid lay, they were poor feather cover, vent cannibalism, footpad dermatitis, keel bone deformation, respiratory disease and roundworms. Feather pecking and cloacal prolapse were most common during late lay. Although differences in hen genetics, farm management practices, and environmental factors could all have affected the results of this study, the information provides a better understanding of hen health in noncage housing systems and could help to identify potential interventions to reduce hen welfare problems.

Symposium: Animal welfare challenges for today and tomorrow.

The increasing separation of the public from production agriculture means there is often a lack of knowledge among consumers about current production practices and a perception that increased productivity and economic efficiency are necessarily associated with a decline in animal welfare. A symposium was organized to present information about animal welfare issues and the challenges they pose for both scientists and the poultry and allied industries. Companion papers provide information about understanding public attitudes and physiological/immunological approaches to welfare assessment, while this paper outlines current and future challenges to egg and meat production and industry responses to those challenges. For broiler chickens, increases in growth rate result in corollary increases in metabolic heat generation and water consumption, leading to the need for continuing improvements in housing, ventilation, and litter management. Stocking densities, lighting programs, muscle myopathies, and use of antibiotics are also areas that require research attention. In the layer industry, the key challenge is housing, with the industry undergoing a shift from conventional cage housing to alternatives like enriched colonies or cage-free. While these alternative systems have hen welfare advantages, there are also welfare disadvantages that require the development of mitigation strategies, and it is also essential to address associated issues including economic, environmental, egg safety, and worker health impacts. Concerns on the horizon include euthanasia of surplus male chicks and spent hens as well as beak-trimming. The humaneness of slaughter methods is an important welfare and consumer confidence issue, and the current regulations for poultry slaughter in the USA are discussed and compared to those for livestock. The poultry and allied industries, including retailers, are responding to these concerns by consulting with experts, developing science-based animal care standards and auditing programs, strengthening training and oversight programs, promoting research, and improving communication channels. In future, intensifying multi-disciplinary research efforts and developing mechanisms to improve communication between scientists and stakeholders, including the public, will be critical to addressing these issues.

The effect of northern fowl mite (Ornithonyssus sylviarum) infestation on hen physiology, physical condition, and egg quality.

The northern fowl mite (NFM),Ornithonyssus sylviarum, is the most common ectoparasite of laying hens in North America. Infestation can cause a reduction in egg production, egg weights, and feed conversion efficiency. However, there is a lack of information on the effects of NFM on hen physiology, physical condition, and egg quality. Singly caged beak-trimmed White Leghorn hens (N=32) were infested with mites at 25 wk of age. The condition of each hen was assessed at wk 0 (infestation) and wk 5 and 7 post-infestation to determine comb temperatures and feather, skin, and comb condition. Heterophil-lymphocyte (H/L) ratios and body weight (BW) were evaluated at wk 0 and wk 1, 3, 5, and 7 post-infestation. Egg weight, egg specific gravity, yolk color, Haugh unit (HU), and eggshell thickness were determined prior to infestation (wk -1) and at 1, 3, 5, and 7 wk post-infestation. The H/L ratio (P<0.0001), HU (P<0.0001), and egg specific gravity (P=0.001) were lowest, and the egg yolk color was lightest (P=0.087) at wk 5, the peak of infestation. At wk 5 and 7, more than 65% of the hens had red skin and more than 75% had scabs on the vent; in addition more than 84% had grey-black vent feathers. There were no effects of infestation on comb color, comb temperature, feather cover, BW, or eggshell thickness. It was concluded that infestation with NFM has negative effects on interior egg quality and hen integument. A decrease in H/L ratio was also observed at the peak of infestation. However, the effects of NFM on the immune system are unclear, and H/L ratio might not be a good stress measure in hens highly infested with NFM.

Relationships between beak condition, preening behavior and ectoparasite infestation levels in laying hens.

The effects of beak condition on ectoparasite populations and preening in laying hens were investigated. Beak-trimmed and beak-intact caged Hy-Line W-36 hens were infested with either chicken body lice or northern fowl mites using a 2×2 factorial design with 4 replicate cages (each containing 2 hens)/treatment: 1) BTL: (beak-trimmed lice-infested); 2) BTM: (beak-trimmed mite-infested); 3) BIL: (beak-intact lice-infested); and 4) BIM: (beak-intact mite-infested). Mite scores and lice numbers were estimated weekly. Hens were video recorded the wk before infestation and at wk 6 and 9 post-infestation. Time spent preening on 6 body areas and in total were analyzed using a repeated measures ANOVA. There was a wk×beak condition interaction for lice loads, with BTL harboring approximately 17 times more lice than BIL from wk 7 to 10 post-infestation (P<0.0001). Beak condition affected mite loads (P<0.0001), with BTM having a higher mite score (3.8±0.26) than BIM (1.4±0.26). At peak infestation, BTL spent more total time preening (P=0.02, s±SE: 232.1±37.6) than prior to infestation (33.9±37.6) and directed their preening behavior towards the vent. In contrast, BIL (73.9±37.6), BTM (9.4±1.6), and BIM (8.6±1.6) did not increase total time spent preening over pre-infestation levels (103.6±37.6, 5.8±1.6, 6.7±1.6 respectively), although BTM did redirect their preening behavior toward the vent. This study confirmed previous studies showing that an intact beak is important for reducing ectoparasite infestations. Preening behavior increased in response to lice infestation, but only in beak-trimmed hens; preening behavior and louse load were correlated at peak infestation. In contrast, mite infestation did not lead to increased preening, and there was no correlation between preening and mite load. However, both lice- and mite-infested hens directed preening behavior predominantly towards the vent where these parasites are typically found.

The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long-term effect on behavior, as evidenced by behavioral changes that persisted despite re-enrichment. Ours is the first study evaluating the relationship between personality dimensions, environment, and abnormal behaviors in an avian species.

Determination of space use by laying hens using kinematic analysis.

Two states in the United States now have legislation requiring that laying hens be provided with sufficient space to perform particular behaviors. To provide a framework for translating these performance standards into a space requirement, kinematic analysis was used to measure the amount of space needed for White Leghorn hens to stand, turn around 180°, lie down, and wing flap. Hyline W-36 hens (n = 9) were marked on the tops of their heads and the tips of both wings and 3 toes with black livestock marker. Each hen was then placed in a floor pen (91.4 × 91.4 cm) and filmed using 2 high-speed cameras. The resulting images were processed using a software program that generated 3-dimensional space use for each behavior. Because none of the hens lay down in the test pen, the 2-dimensional space required for lying was determined by superimposing a grid over videos of the hens lying down in their home cages. On average, hens required a mean area of 563 (± 8) cm(2) to stand, 1,316 (± 23) cm(2) to turn around, 318 (± 6) cm(2) to lie down, and 1,693 (± 136) cm(2) to wing flap. The mean heights used were 34.8 (± 1.3) cm for standing, 38.6 (± 2.3) cm for turning, and 49.5 (± 1.8) cm for wing flapping. However, space requirements for hens housed in multiple-hen groups in cage or noncage systems cannot be based simply on information about the space required for local movement by a single hen. It must also incorporate consideration of the tendency of hens in a flock to synchronize their behaviors. In addition, it must include not just local movement space but also the space that hens may need to use for longer-distance movements to access resources such as food, water, perches, and nest boxes.

Performance on the Hamilton search task, and the influence of lateralization, in captive orange-winged Amazon parrots (Amazona amazonica).

Psittacines are generally considered to possess cognitive abilities comparable to those of primates. Most psittacine research has evaluated performance on standardized complex cognition tasks, but studies of basic cognitive processes are limited. We tested orange-winged Amazon parrots (Amazona amazonica) on a spatial foraging assessment, the Hamilton search task. This task is a standardized test used in human and non-human primate studies. It has multiple phases, which require trial and error learning, learning set breaking, and spatial memory. We investigated search strategies used to complete the task, cognitive flexibility, and long-term memory for the task. We also assessed the effects of individual strength of motor lateralization (foot preference) and sex on task performance. Almost all (92%) of the parrots acquired the task. All had significant foot preferences, with 69% preferring their left foot, and showed side preferences contralateral to their preferred limb during location selection. The parrots were able to alter their search strategies when reward contingencies changed, demonstrating cognitive flexibility. They were also able to remember the task over a 6-month period. Lateralization had a significant influence on learning set acquisition but no effect on cognitive flexibility. There were no sex differences. To our knowledge, this is the first cognitive study using this particular species and one of the few studies of cognitive abilities in any Neotropical parrot species.

The effects of light stimulation during incubation on indicators of stress susceptibility in broilers.

Providing light during incubation has been shown to decrease bilateral physical asymmetry of broilers posthatch, which may indicate that early light stimulation reduces later stress susceptibility. This experiment evaluated the effects of lighting during embryogenesis on other measures of stress responsiveness in broilers. Cobb 500 eggs (n = 1,404) were incubated under 0L:24D, 1L:23D, 6L:18D, or 12L:12D; the light level was 550 lx. The broilers were then raised in floor pens under a 12L:12D lighting regimen, and various stress parameters were measured during wk 3 to 6 of age. There was an effect of incubation lighting regimen on posthatch stress responses. Following 1 h of crating, the change in corticosterone (CORT) concentration was less in the 12L:12D (-0.06 ng/mL, P < 0.05) treatment than all other treatments (pooled mean = 0.24 ng/mL); however, there were no treatment differences in CORT response to adrenocorticotropic hormone administration (pooled mean pre- vs. 1 h postadministration = 17.5 ng/mL, P > 0.05). Anti-keyhole limpet hemocyanin titers were higher in the 12L:12D birds (92,395 units/mL; P < 0.05) than all other treatments (pooled mean = 68,407 units/mL) on d 1 postcrating. Additionally, composite asymmetry scores were lower in the 12L:12D treatment (0.92 mm) than all other treatments (pooled mean = 1.14 mm, P < 0.05). These results demonstrate that providing 12 h of light per day during incubation can reduce the stress susceptibility of broilers posthatch.

An epidemiological approach to welfare research in zoos: the Elephant Welfare Project.

Multi-institutional studies of welfare have proven to be valuable in zoos but are hampered by limited sample sizes and difficulty in evaluating more than just a few welfare indicators. To more clearly understand how interactions of husbandry factors influence the interrelationships among welfare outcomes, epidemiological approaches are needed as well as multifactorial assessments of welfare. Many questions have been raised about the housing and care of elephants in zoos and whether their environmental and social needs are being met in a manner that promotes good welfare. This article describes the background and rationale for a large-scale study of elephant welfare in North American zoos funded by the (U.S.) Institute of Museum and Library Services. The goals of this project are to document the prevalence of positive and negative welfare states in 291 elephants exhibited in 72 Association of Zoos and Aquariums zoos and then determine the environmental, management, and husbandry factors that impact elephant welfare. This research is the largest scale nonhuman animal welfare project ever undertaken by the zoo community, and the scope of environmental variables and welfare outcomes measured is unprecedented.

General Principles for the welfare of animals in production systems: the underlying science and its application.

In 2012, the World Organisation for Animal Health adopted 10 'General Principles for the Welfare of Animals in Livestock Production Systems' to guide the development of animal welfare standards. The General Principles draw on half a century of scientific research relevant to animal welfare: (1) how genetic selection affects animal health, behaviour and temperament; (2) how the environment influences injuries and the transmission of diseases and parasites; (3) how the environment affects resting, movement and the performance of natural behaviour; (4) the management of groups to minimize conflict and allow positive social contact; (5) the effects of air quality, temperature and humidity on animal health and comfort; (6) ensuring access to feed and water suited to the animals' needs and adaptations; (7) prevention and control of diseases and parasites, with humane euthanasia if treatment is not feasible or recovery is unlikely; (8) prevention and management of pain; (9) creation of positive human-animal relationships; and (10) ensuring adequate skill and knowledge among animal handlers. Research directed at animal welfare, drawing on animal behaviour, stress physiology, veterinary epidemiology and other fields, complements more established fields of animal and veterinary science and helps to create a more comprehensive scientific basis for animal care and management.

A system utilizing radio frequency identification (RFID) technology to monitor individual rodent behavior in complex social settings.

Pre-clinical investigation of human CNS disorders relies heavily on mouse models. However these show low predictive validity for translational success to humans, partly due to the extensive use of rapid, high-throughput behavioral assays. Improved assays to monitor rodent behavior over longer time scales in a variety of contexts while still maintaining the efficiency of data collection associated with high-throughput assays are needed. We developed an apparatus that uses radio frequency identification device (RFID) technology to facilitate long-term automated monitoring of the behavior of mice in socially or structurally complex cage environments. Mice that were individually marked and implanted with transponders were placed in pairs in the apparatus, and their locations continuously tracked for 24 h. Video observation was used to validate the RFID readings. The apparatus and its associated software accurately tracked the locations of all mice, yielding information about each mouse's location over time, its diel activity patterns, and the amount of time it was in the same location as the other mouse in the pair. The information that can be efficiently collected in this apparatus has a variety of applications for pre-clinical research on human CNS disorders, for example major depressive disorder and autism spectrum disorder, in that it can be used to quantify validated endophenotypes or biomarkers of these disorders using rodent models. While the specific configuration of the apparatus described here was designed to answer particular experimental questions, it can be modified in various ways to accommodate different experimental designs.

How can social network analysis contribute to social behavior research in applied ethology?

Social network analysis is increasingly used by behavioral ecologists and primatologists to describe the patterns and quality of interactions among individuals. We provide an overview of this methodology, with examples illustrating how it can be used to study social behavior in applied contexts. Like most kinds of social interaction analyses, social network analysis provides information about direct relationships (e.g. dominant-subordinate relationships). However, it also generates a more global model of social organization that determines how individual patterns of social interaction relate to individual and group characteristics. A particular strength of this approach is that it provides standardized mathematical methods for calculating metrics of sociality across levels of social organization, from the population and group levels to the individual level. At the group level these metrics can be used to track changes in social network structures over time, evaluate the effect of the environment on social network structure, or compare social structures across groups, populations or species. At the individual level, the metrics allow quantification of the heterogeneity of social experience within groups and identification of individuals who may play especially important roles in maintaining social stability or information flow throughout the network.

Reverse-translational biomarker validation of Abnormal Repetitive Behaviors in mice: an illustration of the 4P's modeling approach.

The NIMH's new strategic plan, with its emphasis on the "4P's" (Prediction, Pre-emption, Personalization, and Populations) and biomarker-based medicine requires a radical shift in animal modeling methodology. In particular 4P's models will be non-determinant (i.e. disease severity will depend on secondary environmental and genetic factors); and validated by reverse-translation of animal homologues to human biomarkers. A powerful consequence of the biomarker approach is that different closely related disorders have a unique fingerprint of biomarkers. Animals can be validated as a highly specific model of a single disorder by matching this 'fingerprint'; or as a model of a symptom seen in multiple disorders by matching common biomarkers. Here we illustrate this approach with two Abnormal Repetitive Behaviors (ARBs) in mice: stereotypies and barbering (hair pulling). We developed animal versions of the neuropsychological biomarkers that distinguish human ARBs, and tested the fingerprint of the different mouse ARBs. As predicted, the two mouse ARBs were associated with different biomarkers. Both barbering and stereotypy could be discounted as models of OCD (even though they are widely used as such), due to the absence of limbic biomarkers which are characteristic of OCD and hence are necessary for a valid model. Conversely barbering matched the fingerprint of trichotillomania (i.e. selective deficits in set-shifting), suggesting it may be a highly specific model of this disorder. In contrast stereotypies were correlated only with a biomarker (deficits in response shifting) correlated with stereotypies in multiple disorders, suggesting that animal stereotypies model stereotypies in multiple disorders.

Report of the Working Group on Animal Distress in the Laboratory.

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

Animal neuropsychology: validation of the Intra-Dimensional Extra-Dimensional set shifting task for mice.

Research in animal neuropsychology is providing an exciting new generation of behavioral tests for mice that promise to overcome many of the limitations of current high-throughput testing, and provide direct animal homologues of clinically important measures in human research. Set shifting tasks are some of the best understood and widely used human neuropsychological tasks, with clinical relevance to traumatic brain injury, schizophrenia, autism, obsessive compulsive disorder, trichotillomania, and many other disorders. Here we report the first successful modification of a human set shifting neuropsychological task, the Intra-Dimensional Extra-Dimensional (IDED) task, for use with mice. We presented mice with a series of compound discrimination and reversal tasks where one stimulus dimension consistently cued reward. Task performance improved with a new set of compound stimuli, as did reversal performance--indicating the formation of a cognitive-attentional set. We then overtrained a subset of the mice, and presented control and overtrained mice with a new compound discrimination where a novel stimulus dimension cued reward. As is the case in human control subjects, control mice persisted in responding to the now-incorrect stimulus dimension, performing poorly on this extra-dimensional shift compared with the previous intra-dimensional shift, thereby validating the task as a measure of set shifting. Furthermore, overtrained mice were impaired on this extra-dimensional shift compared with controls, further validating the task. The advantages and disadvantages of the IDED task compared to high-throughput approaches are discussed.