Bored at home? - A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice

doi:10.21203/rs.3.rs-1411623/v1

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Bored at home? - A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice

https://doi.org/10.21203/rs.3.rs-1411623/v1

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Boredom is an emotional state that occurs when an individual has nothing to do, is not interested in the surrounding, and feels dreary and in a monotony. While this condition is usually defined for humans, it may very well describe the lives of many laboratory animals housed in small, barren cages. To make the cages less monotonous, environmental enrichment is often proposed. Although housing in a stimulating environment is still used predominantly as a luxury good and for treatment in preclinical research, enrichment is increasingly recognized as a way to improve animal welfare. To gain insight into how stimulating environment influences the welfare of laboratory rodents, we conducted a systematic review of studies that analyzed the effect of enriched environment on behavioral parameters of animal wellbeing. Remarkably, a considerable number of these parameters can be associated with symptoms of boredom. Our findings show that a stimulating living environment is essential for the development of natural behavior and animal welfare of laboratory rats and mice alike, regardless of age and sex. Conversely, confinement and under-stimulation in conventional housing systems has potentially detrimental effects on the mental and physical health of laboratory rodents. We show that boredom in experimental animals is measurable and does not have to be accepted as inevitable.

Recommendations for the husbandry of laboratory animals have been developed primarily with a view to standardizing experimental conditions and providing basic needs like water and food^1,2. The provision of basic needs indeed helps avoiding obvious pain and suffering in laboratory animals, but conserving resources and personnel costs certainly is a main factor in modern animal housing. For the planning of animal experiments, compromises are made between the various interests of researchers, animal caretakers, animal house managers, and animal welfare advocates. The guidelines of the EU-directive for example contains basic recommendations including that highly social animals should be kept in groups and that all laboratory animals should be given the opportunity to develop a wide range of normal behavior by providing a housing condition with sufficient complexity (EU Directive 2010/63). Moreover, species-specific recommendations for rats and mice call for the provision of environmental enrichment to make laboratory animal housing more diverse, but without further defining the type of enrichment (e.g., www.gv-solas.de/fileadmin/user_upload/pdf_publikation/Tierhaltung/hal_201408Tiergerechte-Haltung-Maus.pdf). It is so vague, in fact, that the term has changed a lot in the last few decades^3,4. For example, some of what was described as enriched animal husbandry 25 years ago nowadays just meets the basic recommendations (i.e., a cardboard tube ^5,6). Still, the current housing of most laboratory animals reflects an impoverished environment compared to life in the wild. More specifically, one must assume that the lack of stimuli has far-reaching consequences for the well-being and health status of laboratory animals. In fact, Cait et al. ⁷ showed in a meta-analysis of 214 studies that conventional housing increases morbidity and mortality in research rodents. This is backed up by the here reviewed research on comparing laboratory conventional housing to a more varied enriched housing using more space, social contact, and/or physical items, which conclusively describe positive effects on well-being and behavior of mice provided with enrichment.

Environmental enrichment was initially introduced to laboratory animals for studies investigating the effect of environment on neurobiological parameters and learning behavior⁸. For this very purpose it is still being used, for example, enrichment has been proven to be an effective therapeutic intervention in animal models of various diseases including stroke⁹ and neurodegenerative diseases like Alzheimer's disease¹⁰. Moreover, a stimulating environment improves learning and memory formation and is a potent trigger for neuroplastic events in the adult brain - a process originally thought to occur only in the young developing brain¹¹. In addition to disease models and neurobiological studies, increasing focus has been placed on the effect of stimulating environments on animal welfare. Stress-responses were mitigated under enriched housing conditions and the activity of natural-killer cells was enhanced¹². Expression of abnormal repetitive behaviors (i.e., stereotypies) were reduced in mice living in an enrichment environment^13–17 as were behavioral measures related to anxiety^12,13,18. In summary, most publications indicate that enriched and varied housing conditions improve the wellbeing of laboratory animals. However, due to the low stimuli of conventional housing systems compared to the natural environment, this conclusion might be validly expressed in the opposite sense, that conventional housing of laboratory animals significantly compromises animal welfare and health.

Standard husbandry of laboratory animals in research laboratories is characterized by confinement, monotony and lack of challenge. In humans, such conditions are usually accompanied by a condition known as boredom. Boredom is an emotional state that usually relates to individuals having nothing to do, are not interested in their surroundings, and feel that life is dull and tedious^19,20. This state could also very aptly describe the life of many laboratory animals housed in small barren cages. Few studies have directly addressed the issue of animal boredom so far. However, based on the findings from human studies^21,22, some behavioral abnormalities observed in captive animals can be readily linked to boredom²³.

For example, barbering behavior in animals has recently been related to Trichotillomania ("hair-pulling disorder"), a human disorder reportedly triggered by boredom^24,25. Common abnormalities in captive animals are stereotypies, which are often related to a lack of stimulation in laboratory animals. Stereotypic behavior in mice like wire gnawing/bar- mouthing¹⁵, circling at the cage lid, back- flipping, route tracing, and twirling^13,14 was shown to be decreased under more stimulating enriched housing conditions. Another symptom of human boredom is an altered perception of time, in which time does not seem to pass in monotonous situations²⁶. In animals, this phenomenon can be measured objectively by training them to expect a specific event or reward after a predictable period and measuring their anticipatory behavior after being exposed to monotonous tasks or environments²³. This method was successfully trained in starlings using pecking a key as an anticipatory behavior²⁷. It is reasonable to assume that laboratory rodents also experience such a perceptual shift, but as far as we know this has not been investigated until now.

Since a sufficient form of stimulation is lacking in boring situations, sensation-seeking or stimulus-seeking behavior also occurs in animals²³. This is seen as a form of escape from the unpleasant, boring situation. Indeed, it has been described that it is sometimes of little importance whether the stimulus has a positive or negative valence if interaction is possible at all²⁸. Burn et al. (2020)²⁹ showed stimulus seeking in ferrets as increased contact to negative and ambiguous stimuli compared to a control group which were provided a one hour daily play time. Furthermore, ferrets without playtime spent more time lying awake with their eyes open, screeched more but sat and stood less, than after playtime²⁹. This form of awake inactivity as a form of suboptimal arousal can be seen as an indicator of bored animals as well and was also more apparent under non stimulating housing conditions in mink^28,30 and mice³¹. Moreover, Meagher et al. (2017)³⁰ found increased interest in different external stimuli in mink in non- enriched environments as a form of sensation seeking of potentially bored animals. These two almost opposite extremes of boredom symptomatology - sensation seeking versus awake inactivity - illustrate the multifaceted nature of the expression of boredom and thus the difficult search for a fixed definition for this distressing and damaging emotional condition. In psychology and medicine, boredom is gaining increasing recognition as a potentially harmful emotional state and as a field of research for translational studies^20,32. Regarding animal welfare, boredom becomes a serious concern with an urgent need for research. In this systematic review, we therefore examined the literature on enriched environment with specific regard to the effects of housing conditions on wellbeing in laboratory mice and rats. Moreover, we examine the existing body of literature specifically related to boredom symptoms. By identifying measures of boredom as well as clues to potential cures for boredom in laboratory rodents, we aim to lay the groundwork for addressing this pressing issue in the context of modern animal research.

2.1 Search Strategy

In accordance with PRISMA guidelines, we searched the database WEB OF SCIENCE. WEB OF SCIENCE categories were set to neurosciences, behavioral sciences, veterinary sciences, multidisciplinary sciences, psychology biological and biology for further specialization. Different housing conditions were included as intervention and at least one behavioral observation or test should have been performed as an outcome parameter for animal welfare. For further specialization of the resulting search string boredom and its synonyms were as well included as their respective counterpart. To achieve a high outcome of relevant research papers in the final search, truncations with wildcards and synonyms were used in the search string establishment.

Searchstring:

WOS 2019-07-05, 378 publications

(TS=(boredom OR tedium OR ennui OR tediousness OR stuffiness OR dullness OR boringness OR monotony OR bor* OR monoton* OR motivat* OR stimulat* OR excit* OR activ* OR "affective state*"))

AND TS=(hous* OR husbandry OR "animal keeping" OR environment*)

AND TS=(mice OR mouse OR rat OR rats)

AND TS=(behavior* OR behaviour*)

AND TS=(standard OR conventional OR barren OR restricted OR impoverished)

AND TS=(enrich* OR seminatural OR semi-naturalistic)

Refined by: WEB OF SCIENCE CATEGORIES: (NEUROSCIENCES OR BEHAVIORAL SCIENCES OR VETERINARY SCIENCES OR MULTIDISCIPLINARY SCIENCES OR PSYCHOLOGY BIOLOGICAL OR BIOLOGY)

2.2 Selection of studies and information extraction

The search string resulted in 378 research articles (Fig. 1). Abstract screening was done by three reviewers (PM, UH, KD) using the systematic reviewing online tool SyRF (http://www.syrf.org.uk/). This process decreased the number of research articles to 274. Exclusion criteria included the use of other animals than rats and mice, no behavioral observation or experiment, use of only one housing condition, use of psychoactive drugs, use of a disease or transgenic models. We excluded editorials, conference abstracts, and review papers. We included papers that compared two or more housing conditions contained at least one behavioral observation or experiment with rats or mice.

Three reviewers (PM, UH, KD) independently screened full text and extracted information from eligible studies into a standardized form. Extracted parameters included species, strain, sex, age at the start of the housing period and the beginning of the behavioral experiment, the presence of a focus on animal welfare, the disease/lesion model, genetic modification, psychoactive substances/stimulations, enrichment category (social, object, space of homecage) and description, number of groups including control group and their housing, the mean behavioral outcome parameter and the used behavioral test. Any discrepancies were resolved by consensus. Randomization was done with the sample() function in the statistical computing software R (https://www.r-project.org/).

To keep the analysis up to date during the processing period, the search term was applied again on 24.02.2021 to the database WEB OF SCIENCE. This second search identified 50 new references, which were screened according to the procedure described.

2.3 Categorization and classification of age and durations of housing

Outcome parameters were categorized as follows: social behavior, aggressive behavior, abnormal behavior, affective wellbeing, activity, cognition, nociception, motor function, circadian rhythm, and exploratory behavior. An overview of the behavioral tests used in the studies and the assignment to the categories is shown in Table S1. In addition, we extracted information about glucocorticoid hormones to evaluate effects of housing on stress. However, determination of stress hormones regarding sample source, number, and sampling-time was very heterogeneous. We therefore included glucocorticoids only in the main overview.

For a detailed examination of the effects of enrichment on animal welfare, the results of each study were considered in terms of sex of experimental animals, age of experimental animals, and duration of treatment. For age classification, animals were designated as postnatal from 0 to 21 days of age, adolescent from 21 to 60 days of age, adult from 60 to 750 days of age, and post reproductive from more than 750 days of age³³. Duration of husbandry was classified in short, mid, and long-term housing duration with short defined as 0–30 days, mid with 30–90 days and long-term with more than 90 days.

For an in-depth investigation of boredom, all selected publications were screened again for boredom-specific parameters. Because few studies have explicitly examined boredom in animals, especially laboratory animals, the classification of boredom parameters was based on the symptomatology of human boredom and relevant translatable phenomena in mice and rats. The sources for these parameters were literature on human boredom^21,34 and Charlotte Burn's pioneering review article on animal boredom²³. All studies selected in this systematic review were examined with regard to these parameters. For the examination of the parameter “drug seeking behavior”, the studies related to the use of psychoactive substances that were excluded for the main analysis were re-integrated into this single analysis. Results of this part of the analysis are summarized in Table 1.

2.4 Analysis

Analysis and illustrations were done using the software environment R (version 3.6.3, https://www.r-project.org/, R Foundation for Statistical Computing, Vienna, Austria) and the development software and graphical user interface RStudio (version 1.2.1335, RStudio, Inc., Boston, MA, USA).

To assess the impact of enrichment on the defined categories, it was determined whether the selected studies reported an increase or a decrease in the respective categories; if no change was found, the result was classified as neutral. In the figures, the bars represent the studies that reported an increase, a decrease, or no change in the respective parameter in the corresponding category. The thickness of the bars reflects the amount of identified and investigated studies for this category. The numbers indicate the observed effect of the enrichment as a decimal number. If this value reaches 1, all studies in this category have observed an increase; correspondingly, a decrease if the value reaches − 1. A bar located further to the right of the scale thus indicates an increasing effect of the applied enrichment on the category under consideration. The numbers correspond to the principle of a Likert scale.

Figure 2 shows the parameters that were examined in the context of environmental enrichment. The figure also shows the parameters that were defined as indicators of boredom and explicitly searched for in the publications. There is a large overlap between the factors examined in the studies and the boredom-related parameters. Although boredom is not often explicitly mentioned, this theme clearly resonates in many studies of the effects of enriching housing conditions.

3.1 Increasing number of publications about home cage enrichment.

The absolute number of papers included, classified by year of publication and presence of a research focus on animal welfare, is shown in Fig. 3. Due to the screening date in the beginning of the year 2021, this year is not shown in the bar chart as it is not representing a full year. In 2021, two papers were included in the parameter extraction with none of them focusing on animal welfare. The number of studies investigating the effect of enriched housing on the behavior of mice and rats has increased, especially in the last 10 years, with peaks in 2015/2016 and 2018 with a total of 13 publications. All studies that explicitly aimed to improve the housing conditions of laboratory animals and thus were dedicated to refining animal experiments were categorized as "Focus on animal welfare". Although the absolute number of publications with a focus on animal welfare was slightly increasing over time, its overall proportion is still low.

3.2 Results on reviewed methods and experimental designs

Rats have been used more frequently than mice to study the effects of housing conditions on behavior and for both species, mainly males were examined (Fig. 4). The most frequently used rat strain was Sprague-Dawley (37 references) followed by Wistar (25 references). Seven studies housed Long-Evans rats as experimental animals. Fourteen different strains of mice were studied in the context of environmental enrichment. The most used strains were C57BL/6 (20 references), BALB/C (12 references) and CD-1 mice (9 references).

The enrichment applied in the examined studies was divided into three categories. "Social enrichment" was defined as being housed in a group or provided with a cage partner. When additional space by increasing the homecage size was used to provide enrichment, the category 'size enrichment' was indicated. The "object enrichment" category was assigned when the environment was changed by the introduction of objects of any kind (toys, climbing opportunities, structural elements).

Most studies used a combination of all three types of enrichment in their experiments (75 references). This was followed by a combination of object enrichment and size enrichment of the homecage (33 references). Social enrichment alone (4 references), enrichment of homecage space alone (3 references) and the combination of social and spatial enrichment (2 references) were the least used types of enrichment. Three studies used environmental enrichment in their experiments but did not mention the type.

3.3 A stimulating environment is essential for the development of natural behavior and animal welfare.

Providing animals with an enriched environment substantially improves motor and cognitive skills. Social behaviors and affective state were positively affected, and abnormal behaviors were considerably decreased compared to conventional or barren housed animals, also indicating a positive protective effect. The effects of enrichment on the categories aggressive behavior and activity though remain inconclusive. There is no clear tendency to either increase or decrease of stress hormones in relation to housing conditions (Fig. 5).

3.4 Mice and rats benefit equally from enriched environments

The reported effects of environmental enrichment on animal welfare are largely independent of the animal species compared in this study. Mice and rats benefit equally from enrichment of their living environment (Fig. 6). An exception is aggressive behavior, which decreases in rats while ambiguous results were found in mice when they are kept in an enriched environment. However, the influence of enrichment on aggressive behavior in rats was only investigated in one study using female animals.

3.5 Enriched housing conditions improve the wellbeing of laboratory rats and mice regardless of age

Most of the studies examined were conducted with adolescent animals (91 references). Twenty-five studies used adult animals and 26 studies used postnatal animals. There were no studies on post-reproductive animals. Apart from this discrepancy in the use of animals of different ages, the effects of enrichment on cognition, affective well-being, social behavior, and the development of abnormal behavior proved generally positive for all age groups (Fig. 6). Motor function was positively affected by enrichment but data in postnatal and adult animals are lacking here as well as in post-reproductive animals. Ambiguous results of the effect of enrichment on aggressive behavior, exploratory behavior and activity with an increase, decrease as well as a neutral or no effect could be detected.

3.4 The longer the period of housing in an enriched environment, the higher the benefit to welfare

Most of the included studies applied a medium housing period (30–90 days, 83 references). The most beneficial effect of enrichment was obtained with a long housing duration (more than 90 days, 20 references) but all durations could improve motor function, cognition and affective well-being and exert a protective effect against the development of abnormal behavior (Fig. 7). The effect of enrichment duration on aggressive behavior and activity remained inconclusive with a tendency to an increase in aggressive behavior and activity in a long-term provision of enrichment.

3.5 Enriched housing conditions promote the wellbeing of all genders

Most of the studies examined were performed on males (86 references). Thirty-three studies examined both sexes whereas only 19 studies did experiments on female animals. Enrichment increases cognition, social behavior and motor function and decreases abnormal behavior in female and male animals alike. Regardless of sex, an equal number of studies reported an impairment, a reduction, or no effect on activity. Exploration and aggressive behavior in females decreased with the provision of enrichment. Eight studies examined the effect of enrichment on aggressive behavior in male animals. In four of these studies, an increase in aggressive behavior was observed.

Environmental enrichment has been a popular research topic for some time, not excessively but continually researched. Neuroscience research has provided some fundamental results in this field, elucidating the close relationship of animal housing conditions on the structure and function of the central nervous system. Most published studies use enrichment as an intervention in animal models of various diseases, including stroke^35,36, traumatic brain injury³⁷, and Alzheimer’s disease¹⁰. Although this is a highly exciting field of research, these studies were deliberately not included in this systematic review. This systematic review instead focuses on enriched environment as a means of preventing boredom-like symptoms and improving the welfare of laboratory animals.

While research activity on enriched environments has increased steadily over the years, only a small fraction of the investigated studies dealt specifically with animal welfare. This is perhaps not surprising, since there are various definitions of animal welfare³⁸, let alone a consensus on how to improve it. However, our data show that the proportion of studies with a specific focus on improving the living conditions of laboratory animals in enrichment research is slightly rising. As animal welfare research gains increasing recognition as an established research discipline, the number of research papers in the field will likely continue to grow.

Our analysis shows that rats are used more frequently than mice in enrichment research and that different strains of both species are used. Nevertheless, rats and mice benefit equally from an enriched living environment and there is no evidence that housing conditions affect the welfare of the different strains differently. Females are underrepresented in studies with mice and even more so in studies with rats. Among the studies using mice, 33% reported the use of both sexes, 46% the use of male, and 19% the use of female mice. In the rat studies, 16% used both sexes, 73% used male, and only 10% used female rats. A similar bias toward the use of male subjects has been found in preclinical animal research³⁹. The underrepresentation of female subjects in animal research is based on the belief that females are more variable than males due to their estrous cycle. However, for most applications including behavioral measures, female rodents display no more variation than males do; and female estrus cycles therefore need not necessarily be given special consideration⁴⁰. The underrepresentation of females in animal research is still pervasive, and the scientific understanding of female biology is compromised by these persistent disparities. To address the inadequate inclusion of female animals, the US National Institutes of Health has implemented policies in 2014 that require applicants to indicate their plans for a balance of males and females in preclinical studies in all future applications, unless gender inclusion is not warranted due to strictly defined exceptions⁴¹. The bias towards male subjects in animal research is receiving additional attention due to a plausible implication in the much-discussed translational crisis. Less consideration has so far been devoted to the obvious ethical implications of this gender imbalance. Since no fewer females than males are born in breeding facilities for laboratory animals, the question inevitably arises as to what happens to the "surplus" females³⁸.

Age is another important experimental factor in animal research that is often inadequately considered in experimental design and poorly reported in publication. Animals used in the examined enrichment studies tend to be young. In most of the studies, the housing phase in the enriched cages started at 0–4 weeks of age. In the behavioral tests, many of the animals were then tested at 6–14 weeks of age (Figure S1). This corresponds to the average age of 8–12 weeks at which laboratory animals are usually used in animal research⁴². At this age, many developmental processes are not yet complete. It is therefore important to note that age-related physiological changes can have a major influence on experimental outcomes.

The positive effects of a diversified housing on physical, cognitive, and affective health of laboratory animals have been demonstrated by numerous publications analyzed in this review. Motor function, cognition, affective wellbeing, and social behavior benefited most from enriched housing. A reduction in abnormal behavior was also frequently reported with enriched housing. Since an enriched environment is often associated with more space and/or the provision of a running wheel, animals in these housing conditions clearly have more opportunity for physical activity than animals in confined housing. Mice housed in enriched cage systems outperformed conventionally housed animals on the rotarod, indicating that enrichment stimulates motor coordination and presumably fitness, even when no running wheel or disc is provided⁴³. Numerous studies on animals and humans have evidenced the beneficial influence of physical activity on the musculoskeletal system^44,45. It is therefore a reasonable assumption that keeping laboratory animals in confined cages can harm the bone structure and musculature of laboratory animals.

Interestingly, we could find either any clear increase or decrease of glucocorticoid stress hormones related to the housing conditions. In a recent review, however, it was suggested that conventional laboratory housing comes along with chronic stress⁷. Instead of a chronic increase in stress hormones, we propose that conventional housing may rather reduce the capacity of the stress axis to cope with environmental challenges and that the health impairments result from constant understimulation.

The effects of a stimulus-rich environment on cognition and affective wellbeing are well documented and there is accumulating evidence for potential underlying brain structures and neurophysiological mechanisms. These extend from brain region volume and morphology to neuron complexity and excitability, adult neurogenesis, synaptic plasticity, and a plethora of molecular responses including gene-environment interactions, inflammation, and trophic factors^46–49. Many of these effects are likely linked to the increased physical activity associated with an enriched housing. However, there are processes that are directly attributable to the stimulative elements of enrichment. These include the successful differentiation and long-term survival of newly formed neurons during neurogenesis, processes that can be clearly distinguished from the proliferation of neural cells, which in turn is facilitated in particular by physical activity⁵⁰.

In the studies reviewed, a variety of housing, bedding, and nesting materials, as well as various items or any combination thereof, were used as enrichment. Historically, all additions to housing cages were considered enrichment. In this way, "enrichment" became an umbrella term for a variety of shelters, bedding and nesting materials, and miscellaneous items, or any combination thereof, and lacked a general theoretical framework for what should be considered enrichment⁴. This is also reflected in the studies reviewed. In most publications, a combination of social, object and spatial enrichment was used (Table S2). Because of the widespread simultaneous use of all types of enrichment, there is no clear consensus on which form is most effective in preventing housing-specific behavioral disorders.

Table 1

**Overview of publications examining boredom related parameters and the respective outcome.** The table is sorted showing the boredom related behaviors with the largest number of publications first. The publications investigating the specific behaviors are sorted by year ascending in order to show actual trends in this field of research.
Boredom related parameter	Publications	Outcome
depressive like behavior	Pare & Kluczynski (1997) ⁵¹ Branchi et al. (2006) ⁵² Abramov et al. (2008) ⁵³ Brenes et al. (2008) ⁵⁴ Brenes et al. (2009) ⁵⁵ Silva et al. (2011) ⁵⁶ Simpson et al. (2012) ⁵⁷ Ros-Simo & Valverde (2012) ⁵⁸ Yildirim et al. (2012) ⁵⁹ Kalliokoski et al. (2013) ⁶⁰ Nishijima et al. (2013) ⁶¹ Cao et al. (2014) ⁶² Mosaferi et al. (2015) ⁶³ Arndt et al. (2015) ⁶⁴ Fureix et al. (2016) ³¹ Nip et al. (2019) ⁶⁵	dec inc neut dec dec neut neut inc inc inc neut dec dec dec dec dec
drug-seeking behavior	Xu et al. (2007) ⁶⁶ El Rawas et al. (2009) ⁶⁷ Chauvet et al. (2011) ⁶⁸ Ranaldi et al. (2011) ⁶⁹ Smith & Pitts (2011) ⁷⁰ Chauvet et al. (2012) ⁷¹ Turner et al. (2014) ⁷² Peck et al. (2015) ⁷³ Bahi (2017) ⁷⁴ Li & Frantz (2017) ⁷⁵ Ewing & Ranaldi (2018) ⁷⁶ Khalaji et al. (2018) ⁷⁷ Arndt et al. (2019) ⁷⁸ Haider et al. (2019) ⁷⁹ Garcia & Cain (2020) ⁸⁰	dec dec dec dec dec dec dec dec dec dec dec dec neut dec dec
stereotypic behavior	Würbel et al. (1998) ¹⁵ Callard et al. (2000) ⁸¹ Olsson & Sherwin (2006) ⁸² Tilly et al. (2010) ⁸³ Latham & Mason (2010) ⁸⁴ Jones et al. (2011) ⁸⁵ Yildirim et al. (2012) ⁵⁹ Hajheidari et al. (2015) ⁸⁶ Joshi & Pillay (2016) ⁸⁷ Fureix et al. (2016) ³¹ Joshi & Pillay (2018) ⁸⁸ Bailoo et al. (2018) ¹³	dec dec dec dec dec dec dec neut dec dec neut dec
novelty seeking behavior	Roy et al. (2001) ⁸⁹ Pietropaolo et al. (2004) ⁹⁰ Cain et al. (2006) ⁹¹ Franks et al. (2013) ⁹² Berardo et al. (2016) ⁹³ Faraji et al. (2018) ⁹⁴ Sparling et al. (2018) ⁹⁵ Rabadan et al. (2019) ⁹⁶ Vazquez-Sanroman et al. (2021) ⁹⁷	dec dec dec inc inc inc dec inc dec
Inactive but awake	Olsson & Sherwin (2006) ⁸² Fureix et al. (2016) ³¹	dec dec
motivation for stimulation	Holm & Ladewig (2007) ⁹⁸ Makowska & Weary (2016) ⁹⁹	dec dec
risk proneness	Berardo et al. (2016) ⁹³	inc
escape behavior	-	-
hair pulling	-	-
time perception	-	-

Enriched environment alleviates boredom-like symptoms in laboratory animals

Some of the outcomes extracted in this review may be directly related to boredom in laboratory animals. These included abnormal behaviors like stereotypic, hyperactivity, and inactive-but-awake behavior, as well as novelty-seeking, drug-seeking, and depressive like behavior. Sixteen included publications investigated depressive like behavior in connection with environmental enrichment. This was mostly done with the forced swim test. The results suggest a differential effect, but the most recent publications show a decrease in depressive-like behavior in enriched housed animals. Fifteen publications were associated as studies on drug-seeking behavior. Here, a clearly positive effect of environmental enrichment can be observed throughout. Findings from the twelve studies that examined stereotypic behavior in mice and rats were similar. There was an overall decrease of stereotypic behavior under enriched housing conditions. Although the occurrence of stereotypic behavior appears to be a multifactorial event in animals^15,16, it can be observed more frequently under barren restrictive housing conditions¹⁰⁰ and has been shown to be reduced by the use of enrichment in zoo animals¹⁰¹. Burn (2017)²³ argued that stereotypic behaviors increase under monotonous situations, if the behavior in general has not become highly perseverative yet and names abnormal repetitive behaviors as a potential measurable boredom parameter in captive animals.

Ten publications dealt with novelty-seeking behavior in the broadest sense. This parameter is often investigated with the open field test or the object recognition test, but also by observing the behavior or activity in newly presented home cages. This broad field of tests makes a clear delineation of this parameter in relation to boredom complicated. This also results in an ambiguous effect of environmental enrichment on novelty seeking behavior.

Very poorly represented are the boredom parameters inactive but awake, motivation for stimulation, and risk proneness. These were examined in five publications showing that these characteristics, which closely relate to human boredom, are positively influenced by environmental enrichment. However, Berardo et al. (2016)⁹³ noted an increase in risk proneness. With only one publication in our body of literature, this statement should be viewed with caution.

Escape behavior, hair pulling, or a possible shift of time perception were not examined by any publication. Overall, it must be noted that in only a few cases boredom is specifically mentioned at all.

Conclusion

Our findings show that a stimulating environment is essential for the development of natural behavior and animal welfare of research rodents. They also indicate that confinement in conventional housing systems has potentially detrimental effects on animal welfare. Chronic boredom as a consequence of living in a barren and confined environment poses a health risk to laboratory animals and thereby also limits their validity as model organisms for biomedical research. A stimulating living environment sustains the wellbeing of laboratory rats and mice alike, regardless of age and sex. Although a longer period of housing might be more beneficial, even a short period in a stimulating environment improves essential parameters of animal welfare. Providing animals with adequate space, social contact and a stimulating environment should not be considered a luxury or a treatment, but a necessity to ensure mental and physical health and the expression of natural behaviors.

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No competing interests reported.

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Bored at home? - A systematic review on the effect of environmental enrichment on the welfare of laboratory rats and mice

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Abstract

Figures

1. Introduction

2. Material And Methods

2.1 Search Strategy

2.2 Selection of studies and information extraction

2.3 Categorization and classification of age and durations of housing

2.4 Analysis

3. Results

3.1 Increasing number of publications about home cage enrichment.

3.2 Results on reviewed methods and experimental designs

3.3 A stimulating environment is essential for the development of natural behavior and animal welfare.

3.4 Mice and rats benefit equally from enriched environments

3.5 Enriched housing conditions improve the wellbeing of laboratory rats and mice regardless of age

3.4 The longer the period of housing in an enriched environment, the higher the benefit to welfare

3.5 Enriched housing conditions promote the wellbeing of all genders

4. Discussion + conclusion

Enriched environment alleviates boredom-like symptoms in laboratory animals

Conclusion

References

Additional Declarations

Supplementary Files

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