Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and why

Harro, Jaanus

doi:10.1016/j.bbr.2017.10.016

Cited by 91 publications

(53 citation statements)

References 202 publications

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“…36 In the present study, no difference in weight gain was detected because of housing conditions, whereas controversial results have been reported by others. 55 We did not see any significant difference in expression of directed exploration towards conspecific (a same-sex, unfamiliar mouse) during the social approach test, whereas others have shown that history of housing in the IVC increased social activity. 37 On the other hand, the housing system did not have any impact on growth in male rats.…”

Section: Discussioncontrasting

confidence: 63%

“…The discrepancy between the results of the LD box and OF (and in general, between different "unconditioned," "exploratory" tests for anxiety-like behavior) may be because of differences in the strength and type of aversive stimulation (bright light, openness, height etc.). 55 We did not see any significant difference in expression of directed exploration towards conspecific (a same-sex, unfamiliar mouse) during the social approach test, whereas others have shown that history of housing in the IVC increased social activity. 48 The observed strain differences in activity and social preference were largely corresponding to the earlier comparisons.…”

Section: Discussioncontrasting

confidence: 63%

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Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Åhlgren

Võikar

2019

Genes Brain and Behavior

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Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6 weeks (since 4 weeks of age) before behavioral testing. The tests addressed exploratory, anxiety‐like and stress‐related behavior (light‐dark box, open field, forced swim test, stress‐induced hyperthermia), social approach and species‐specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light‐dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well‐known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom‐line is that the environmental conditions should be described explicitly in all publications.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussioncontrasting

confidence: 63%

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Åhlgren

Võikar

2019

Genes Brain and Behavior

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“…In addition, anxiety-like behavior was higher in the mice from CRL as compared to the other two vendors. Although widely used, the conventional tests for unconditioned anxiety have often produced contradictory findings, dependent on the laboratory environment 33,81 . Nevertheless, our finding of reduced anxiety and higher activity shown by the B6J mice is in line with several other reports 48,75,82,83 .…”

Section: Discussionmentioning

confidence: 99%

Experiments done in Black-6 mice: what does it mean?

Åhlgren

Võikar

2019

Lab Anim

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Low replicability of animal experiments is perceived as a major hurdle in the field of biomedicine. Attempts to enhance the replicability and to reduce the variability in basic research has led to a recommendation to use isogenic mice. The C57BL/6 strain has evolved as a gold standard strain for this purpose. However, the C57BL/6 mice are maintained as sub-strains by multiple vendors. Evidence exists that the subtle differences between these mouse lines have not been systematically investigated and are often ignored. In the present study, we characterized the female mice of two closely related sub-strains (C57BL/6J and C57BL/6N) from three vendors in Europe (Charles River Laboratories, Envigo, Janvier Labs) in a battery of behavioral tests. Our data show and confirm substantial behavioral differences between the C57BL/6J and C57BL/6N mice. Importantly, the sub-strain differences were largely affected by the origin of animals, as a significant effect of vendor or interaction between the sub-strain and vendor occurred in all tests. This work highlights the importance of adhering to precise international nomenclature in all publications reporting the animal experiments. Moreover, the generalization of research findings from a single mouse sub-strain can be seriously limited due to genetic drift and environmental variables at different vendors. However, generalizability can be enhanced by heterogenization of samples by including the animals of different substrains. These issues need to be seriously considered for improving reproducibility, replicability and translational potential of the mouse models.

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“…In rodents, the OF apparatus typically consists of a circular or rectangular arena (Denenberg, 1969;Harro, 2018) to measure locomotion (e.g., the number of squares crossed or total distance traveled) and anxiety-like center avoidance (e.g., entries or time spent in center vs. periphery). Stressed/anxious animals decrease the exploration and increase time spent in the periphery of the apparatus (thigmotaxis) (Denenberg, 1969;Harro, 2018). Similar to rodents, both larvae and adult zebrafish display characteristic patterns of exploration, with prominent thigmotaxis (Ahmad & Richardson, 2013;Stewart, Gaikwad, Kyzar, & Kalueff, 2012), suggesting that spatiotemporal strategies of exploration may be evolutionarily conserved across vertebrate species (Stewart et al, 2012).…”

Section: Stress/anxiety-like Behaviormentioning

confidence: 99%

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

Abreu

Maximino

Banha

et al. 2019

J of Neuroscience Research

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Experimental animal models are a valuable tool to study the neurobiology of emotional behavior and mechanisms underlying human affective disorders. Mounting evidence suggests that various aquatic organisms, including both vertebrate (e.g., zebrafish) and invertebrate (e.g., crayfish) species, may be relevant to study animal emotional response and its deficits. Ideally, model organisms of disease should possess considerable genetic and physiological homology to mammals, display robust behavioral and physiological responses to stress, and should be sensitive to a wide range of drugs known to modulate stress and affective behaviors. Here, we summarize recent findings in the field of zebrafish‐ and crayfish‐based tests of stress, anxiety, aggressiveness and social preference, and discuss further perspectives of using these novel model organisms in translational biological psychiatry. Outlining the remaining questions in this field, we also emphasize the need in further development and a wider use of crayfish and zebrafish models to study the pathogenesis of affective disorders.

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Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and why

Cited by 91 publications

References 202 publications

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Housing mice in the individually ventilated or open cages—Does it matter for behavioral phenotype?

Experiments done in Black-6 mice: what does it mean?

Emotional behavior in aquatic organisms? Lessons from crayfish and zebrafish

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