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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Session 5 Environmental Enrichment Issues
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Enriching the Housing of the Laboratory Rodent: How Might It Affect Research Outcomes? William T. Greenough and Ann Benefiel This presentation focuses on the research cost-benefit aspect of enrichment of housing conditions for laboratory rats and mice. The choice of this subject emerged because the session organizers requested a presentation on “laboratory animal housing enrichment” and included the following in their letter of charge: The workshop will…focus…on identifying gaps in the current knowledge in order to encourage future research endeavors, assessing potential financial and outcome costs of unscientifically-based regulations on facilities and research, and determining possible negative impacts of arbitrary regulations on animal welfare. The basic view put forth herein is that caution is warranted in the adoption of environmental enrichment procedures, because they may complicate interpretation of research results. We begin by briefly discussing the history of what has come to be called “enriched housing.” The first description of an effect of enhanced living conditions on behavior as an indication of altered brain function was the work of Hebb (1949), who compared rats that he reared as “pets” in his home with counterparts reared under normal laboratory conditions (an experiment unlikely to be repeated, given current regulations regarding research animal housing!). Hebb reported that the home-reared rats were superior to the laboratory rats on complex problem-solving tasks and that they continued to move ahead as they were tested on successive
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop tasks. Subsequently, students of Hebb or others inspired by him repeated the basic finding (in the laboratory), that a more stimulating rearing environment enhanced performance on complex learning tasks (e.g., Bingham and Griffiths 1952; Forgays and Read 1962). Subsequently, Krech and colleagues (1960) reported effects of a similar rat housing environment, for which they adopted the term “enriched,” on measures of the activities of enzymes involved in metabolism relating to cholinergic synaptic transmission. This program led to the discovery that some regions of the cerebral cortex were actually heavier and thicker in the “enriched condition” (EC) rats compared with “impoverished condition” (IC) rats kept in barren individual cages (Diamond and others 1966). Research stimulated by theirs triggered the first report of altered dendritic branching (Holloway 1966), although that paper used methods that were inadequate to quantify dendritic branching. Research on the details of changes induced by such experiences, and that of a number of others, was inspired by the work of Rosenzweig and colleagues. For purposes of this illustration, the work of the Greenough laboratory is selectively emphasized here. An early replication of the Holloway (1966) study using quantitative methods (Volkmar and Greenough 1972) indicated that the dendritic branching of neurons in the rat visual cortex was altered in EC versus IC rats and that “social condition” rats housed in pairs in standard laboratory cages (SC) were intermediate, often differing statistically from both EC and IC rats. This latter result suggests that the more minimalist rodent enrichment procedures such as social housing, which are common in European laboratories and becoming more so in laboratories in the United States now, may actually bring about subtle but detectable changes in the brain. The enriched environment used by the Greenough laboratory, although likely falling short of Hebb’s home is, by contrast, a very complex arrangement of objects for play and exploration as Figure 1 indicates. The effects of these different environments are not restricted to the brain and to the behavior it enables. Significant peripheral somatic differences exist between rats housed in EC and those in IC, which could interact with various sorts of treatments or affect responses to edible reinforcements (Black and others 1989). These differences include, in rats in our laboratory, (1) greater body weight in IC than in EC rats, accompanied by (2) greater food consumption in the ICs, (3) more rapid maturation of the long bones in IC versus EC rats, (4) sometimes greater adrenal to body weight ratios in EC versus IC rats, (5) a higher kidney to body weight ratio in the EC group, and (6) a lower thymus to body weight ratio in the ECs (with no indication of diminished EC immune competence; Black and others 1989). The fact that the organ weight ratios differ in both directions (EC > IC and IC > EC) suggests that they do not reflect merely
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop FIGURE 1 Enriched rat cage. the relatively lower body weights of the ECs. The goal here is not to try to explain why these differences occur, but rather to illustrate that a variety of experimental measurements could be affected by differences of this sort. Hence, on the basis of peripheral measures alone, utilizing rats exposed to enriched housing in other experiments could generate confounded results, and certainly switching from nonenriched to enriched animals could generate changes in experimental outcomes. It should also be noted that male and female rats can differ in their responses to enriched environments (e.g., Juraska 1991, 1998). Thus, basic somatic physiological processes are affected by rearing environment complexity, which can affect research outcomes if those processes are or affect variables of interest, and caution is warranted in introducing novel degrees of environment complexity or “enrichment” into ongoing research paradigms. The brain effects of EC are even more profound. Neurons and their synapses, vasculature, and the two most prominent types of glial cells all are dramatically affected by exposure to an enriched environment. In visual cortex the number of synapses per neuron is 20 to 25% greater in EC rats compared with those in IC, with rats socially housed in cages typically little different from individually housed rats (Turner and
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Greenough 1985). This effect is supported by equally substantial increases in the size of the dendritic fields of neurons (Volkmar and Greenough 1972). Synapse morphology and architecture are also different in EC versus IC rats (Jones and others 1997; West and Greenough 1972). The volume of capillary per neuron is similarly selectively increased in EC rats (Black and others 1987), presumably in part to “power” the increased numbers of synapses, a substantial fraction of which are closely associated with mitochondria on the presynaptic side. Astrocytes, which serve to optimize many metabolic functions of neurons, and can be identified by the presence of their characteristic glial fibrillary acidic protein, are increased in both size and number in EC rats (Sirevaag and Greenough 1991). Moreover, synapses in EC rats are more completely covered by fine astrocytic processes than in IC rats (Jones and Greenough 1996). The other macroglial cell type, the oligodendrocyte that gives rise to the axonal myelination that enhances the speed of conduction of nerve impulses, is also affected by environment enrichment: EC rats have more myelinated axons in the corpus callosum than IC rats (Juraska and Kopcik 1988). All of the foregoing findings have been demonstrated in visual cortex (or connecting callosum), and many effects have also been demonstrated in other brain regions. Taken as a whole, these results indicate that the properties of most cell types and the ways in which they relate to each other in the brain may be altered by the housing environment. Most of these effects also occur in rats put into enriched environments for the first time as adults. Most rats used in research are purchased from suppliers as young adults, typically shortly after they reach the point of sexual maturity, and are used as quickly as possible after they have become accommodated to their new surroundings, in an effort to minimize cost. If the rats were made to accommodate to an enriched laboratory environment, their bodies and brains might be in a state of relative physiological and structural turbulence at just the time they were expected to be ready to participate in experiments. Clearly research on or involving these variables will be affected, and research on other interacting variables might also be affected in unpredictable ways. The mechanisms mediating these effects are largely unknown. Neurotrophic factors such as “brain-derived neurotrophic factor” are known to be altered by environmental variations such as enrichment and exercise (Klintsova and others, submitted; Oliff and others 1998; A.Y. Klintsova, E. Dickson, R. Yoshida, and W.T. Greenough, manuscript in preparation), and these factors may well be a part of the process that generates the responses in brain physiology and structure in response to altered environmental conditions. This further complicates the stability of the background against which experimental effects are to be measured. A novel finding that can be discussed only after it is accepted for
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop publication is Richard Smeyne’s finding that the drug MPTP, which kills catecholamine neurons in the substantia nigra in humans and in conventionally housed rats, does not result in similar neural damage when rats are housed in an enriched environment. Although this finding, of course, suggests important therapeutic directions, it also illustrates the complications that might be induced in a well-developed paradigm by the sudden insertion of enriched housing procedures. Numerous institutions, including my own, have recommended or even mandated enrichment procedures for laboratory rodents recently. In the case of my university, where group housing or the insertion of novel objects into the cage is mandated, a nonscientific poll of principal investigators using rodents found that only I was aware of this policy, despite the fact that those procedures were being applied to their animals at the time I asked them the question. Certainly they did not seem to have been asked whether they thought these procedures might interfere with their research, despite a clear policy guideline with regard to the following statement: “Investigators who must singly cage animals and feel that enrichment materials may confound their research objectives must provide justification.” Enrichment appears to have been accepted as a “good thing,” with little consideration of its possible effects on experimental outcomes. Taken literally, this University of Illinois policy might make it difficult to determine effects of enrichment that one did not know to exist. There is also tacit acceptance that group housing is superior to individual housing despite data that call into serious question whether this is true (Bartolomucci and others 2003). Several presentations at the current meeting seemed similarly to espouse such a view. Perhaps most disconcerting is the arbitrary assumption that enrichment is better for the animals, with little data to support this assumption beyond the fact that the animals attend to enrichment objects and appear to play more vigorously when such objects are present. It appears in this case, as in the case of several other presentations at this workshop, that the animals’ preferences are being allowed to drive, if not dictate, the issue of what constitutes enrichment. In this regard, it is of value to note that animals’ preferences may not be the ideal guideline to what is of most value to them. In earlier research on addiction, which would probably not be permitted today, it was found that rats and monkeys given unrestricted or nearly unrestricted access to drugs of abuse (cocaine, amphetamine, methamphetamine, and alcohol) would self-administer these drugs within 1 month to the point of cessation of eating, refusal of hand-fed treats, and in many cases until dead, or near enough to death that researchers removed them from the experiment and provided life-saving measures to keep them alive (e.g., Johanson and others 1976; Pickens and Thompson 1971). This and similar findings in other
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop self-selection domains suggests that the animals’ judgments are not always in synchrony with what appears optimal to their health (e.g., Galef and Beck 1990). Thus we propose the following recommendation regarding the sudden and arbitrary insertion of environmental enrichment procedures into ongoing research: Caution is warranted. We should not assume that enrichment will not affect our research measurements or outcomes unless demonstrated otherwise. And we should not mandate enrichment of animals engaged (or to be engaged) in a research protocol unless the protocol has been explicitly shown not to be affected by the enrichment procedure to be used (or the effects are known and taken into account). Finally, just as we should use caution in generalizing from humans to mice about what we believe is best for a mouse or a human (see “To a mouse…” by R. Burns [Douglas 1993]), we should also use caution when we generalize across more closely related species, until an experimental basis for doing so has been established. Still thou art blest, compar’d wi’ me The present only toucheth thee: But, Och! I backward cast my e’e. On prospects drear! An’ forward, tho’ I canna see, I guess an’ fear! And finally, The best-laid schemes o’ mice an‘ men Gang aft agley —Robert Burns REFERENCES Bartolomucci, A., Palanza, P., Sacerdote, P., Ceresini, G., Chirieleison, A., Panerai, A.E., Parmigiani, S. 2003. Individual housing induces altered immuno-endocrine responses to psychological stress in male mice. Psychoneuroendocrinology 28:540-558. Bingham, W.E., and W.J. Griffiths, Jr. 1952. The effect of different environments during infancy on adult behavior in the rat. J Comp Physiol Psychol 45:307-312. Black, J.E., Sirevaag, A.M., Greenough, W.T. 1987. Complex experience promotes capillary formation in young rat visual cortex. Neurosci Lett 83:351-355. Black, J.E., Sirevaag, A.M., Wallace, C.S., Savin, M.H., Greenough, W.T. 1989. Effects of complex experience on somatic growth and organ development in rats. Dev Psychobiol 22:727-752. Diamond, M.C., Law, F., Rhodes, H., Lindner, B., Rosenzweig, M.R., Krech, D., Bennett, E.L. 1966. Increases in cortical depth and glia numbers in rats subjected to enriched environment. J Comp Neurol 128:117-125.
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Douglas, W.S., ed. 1933. Collected Works of Robert Burns. London: Taylor & Francis Books Ltd. Forgays, D.G., and J.M. Read. 1962. Crucial periods for free-environmental experience in the rat. J Comp Physiol Psychol 55:816-818. Galef, B.G., and M. Beck. 1990. Diet selection and poison avoidance by mammals individually and in social groups. In: Handbook of Behavioral Neurobiology, Vol. 10, Neurobiology of Food and Fluid Intake. p. 329-349. Hebb, D.O. 1949. The Organization of Behavior. New York: John Wiley & Sons. Holloway, R.L. 1966. Dendritic branching: Some preliminary results of training and complexity in rat visual cortex. Brain Res 2:393-396. Johanson, C.E., Balster, R.L., Bonese, K. 1976. Self-administration of psychomotor stimulant drugs: The effects of unlimited access. Pharmacol Biochem Behav 4:45-51. Jones, T.A., and W.T. Greenough. 1996. Ultrastructural evidence for increased contact between astrocytes and synapses in rats reared in a complex environment. Neurobiol Learning Mem 65:48-56. Jones, T.A., Klintsova, A.Y., Kilman, V.L., Sirevaag, A.M., Greenough, W.T. 1997. Induction of multiple synapses by experience in the visual cortex of adult rats. Neurobiol Learning Mem 68:13-20. Juraska, J.M. 1991. Sex differences in “cognitive” regions of the rat brain. Psychoneuroendocrinology 16:105-119. Juraska, J.M. 1998. Neural plasticity and the development of sex differences. Ann Rev Sex Res IX:20-38. Juraska, J.M., and J.R. Kopcik. 1988. Sex and environmental influences on the size and ultrastructure of the rat corpus callosum. Brain Res 450:1-8. Krech, D., Rosenzweig, M.R., Bennett, E.L. 1960. Effects of environmental complexity and training on brain chemistry. J Comp Physiol Psychol 53:509-514. Oliff, H., Berchtold, N., Isackson, P., Cotman, C. 1998. Exercise-induced regulation of brain-derived neurotrophic factor (BDNF) transcripts in the rat hippocampus. Mol Cell Res 61:147-153. Pickens, R., and T. Thompson. 1971. Characteristics of stimulant drug reinforcement. In: T. Thompson, ed. Stimulus Properties of Drugs. New York: Appleton-Century-Crofts. p. 172-192 . Sirevaag, A.M., and W.T. Greenough. 1991. Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments. Brain Res 540:273-278. Turner, A.M., and W.T. Greenough. 1985. Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res 329:195-203. Volkmar, F.R., and W.T. Greenough. 1972. Rearing complexity affects branching of dendrites in the visual cortex of the rat. Science 176:1445-1447. West, R.W., and W.T. Greenough. 1972. Effect of environmental complexity on cortical synapses of rats: Preliminary results. Behav Biol 7:279-284.
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Search for Optimal Enrichment Timo Nevalainen Recently a Council of Europe (CoE) expert group emphasized the need for environmental enrichment and group housing as refinements for all laboratory species unless there are scientific or veterinary reasons not to do so (Hansen and others 1999). This emphasis is part of the revision of CoE Appendix A, in which species-specific recommendations serve as a starting point in the choice of enrichment. Indeed, the questions are not whether to use but how to use enrichment, and how far it should be regulated. Enrichment as such is unfortunately a poorly defined entity, which can be considered to include, for example, group housing, a variety of added items into cages, and even bedding. If this wide definition is accepted, we all will be using enrichment. This variety and the fact that most of us practice our own enrichment make it very difficult or even impossible to draw general conclusions on the effects of enrichment, which adds to the confusion. Overall, the situation is partly out of hand, and corrective action is desperately needed. We often refer to harmonization as the ultimate goal of international cooperation. How does harmonization relate to enrichment requirements, ethics, and science? In this context, environmental enrichment should be seen as the minimum standard, below which no one is allowed to operate. Well above the minimum standard, there should be an area of excellence, where ideals of ethics and science are the driving forces. Any refinement in housing to improve animal welfare requires:
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop scientific validation that the refinement is truly beneficial for the animals (efficacy) that the refinement does not detract from the scientific integrity (safety). In other words, one should always ask whether a refinement or enrichment has value and whether it hurts science. These factors must be seen as the key criteria of optimal enrichment. The main emphasis of the European guidelines, as well as other guidelines, is on animal welfare, and much less on safeguarding scientific integrity. But how can one compare results from experiments performed in different laboratories when variable environmental enrichment strategies are used throughout the world? Three different approaches to enrichment strategies can be seen. Some people think that anything can be used, and they have long lists of items of various origins. Others practice a precautionary principle with items that have no or poor scientific basis. They try to determine whether there is a potential danger of scientific interference and then act accordingly. A third approach is to use only the enrichment items based on scientific evidence to show both efficacy and safety. This last approach is considered too cynical by others. Enrichment has been shown to change the animal’s behavior and physiology, which are indeed the main goals of the practice. But this alteration also means that the animals are not the same as those used in earlier experiments. This result gives rise to the concern that the scientific data from earlier studies may—at least partly—have become useless. The revision of Appendix A states that enrichment may be omitted if there is a welfare, veterinary, or scientific reason to do so. Interference with an experimental outcome could be an example of a scientific reason and fighting between incompatible animals a veterinary reason. Inappropriate enrichment may result in mortality, morbidity, aggression, and overt stress. All of these results are expressions of a compromised welfare. Selection of materials to be used as enrichment in cages is critical, because some substances may cause interference with well-being and experimental results. Bedding made from soft wood can contain high concentrations of volatile compounds, especially - and -pinenes, causing major changes in liver microsomal enzyme activity. A study published 7 years ago showed that even then many commonly used types of bedding contained many organic volatile compounds, and that autoclaving decreased concentrations to a fraction of the original values (Nevalainen and Vartiainen 1996). If enrichment items are made of organic materials, they should meet the same chemical criteria as bedding. When we compared 15 beddings
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Enrichment for rodents and rabbits (FELASA 2003). The terms of references for the group read as follows: “How to standardize enrichment in rodents and rabbits with essential species-specific needs, needs of gender and life stage and animal welfare (defined as functioning and feeling well) are guaranteed and interference with studies minimized.” We may try to start with a commonsense approach: What are the things that should not be done with enrichment? One should change enrichment as seldom as possible, like one would change the type of diet and bedding, and never within a study. One should prefer a truly inert or a no-new-materials practice. Perhaps we should aim at an “enrichment profile,” starting from the breeder and continuing to the completion of the experiment. Furthermore, one should look for changes in the variance of results and for deleterious effects (e.g., fighting) on animal welfare. Standardization in this context means that there should be a limited number of standardized, efficient, and safe species-specific enrichments. Obviously, this task is challenging and much easier said than done. Best practice should be based on scientific data and aim well beyond harmonization. Regulations, which may be difficult to update regularly, should leave space for adjustments in best practice. There are urgent legal, ethical, and scientific expectations for guidelines on optimal and standardized enrichment. REFERENCES FELASA [Federation of European Laboratory Animal Science Associations]. 2003. FELASA Working Group on Standardization of Enrichment (http://www.felasa.org/working/stenr.html). Hansen, A.K., Baumans, V., Elliot, H., Francis, R., Holgate, B., Hubrecht, R., Jennings, M., Peters, A., Stauffacher, M. 1999. Future principles for housing and care of laboratory rodents and rabbits. Report concerning revision of the Council of Europe Convention ETS 123 Appendix A concerning questions related to rodents and rabbits issued by the Council’s working group for rodents and rabbits. Part A, Actions and proposals of the working group. Meller, A., Laine, O., Voipio, H-M., Vartiainen, T., Nevalainen, T. 2003. Volatile organic compounds in animal bedding and enrichment items. (Abstract.) Presented at the 9th FELASA Symposium held in Nantes , France, June 14-17, 2004. Nevalainen, T., and T. Vartiainen. 1996. Volatile organic compounds in commonly used beddings before and after autoclaving. Scand J Lab Anim Sci 23:101-104. Nevalainen, T.O., Nevalainen, J.I., Guhad, F.A., Lang, C.M. 2003. Pair housing of rabbits and variation in serum chemistry. (Abstract.) Presented at the AALAS 2003 National Meeting, Seattle, WA, USA, October 12-16, 2003.
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Environmental Enrichment Issues: Mice/Rats/Rabbits Leaders: John G.Vandenbergh and Vera Baumans Rapporteurs: Primary, Jennifer Obernier; Secondary, Stephen W. Barthold The informal introductory comments of Drs. Baumans and Vandenbergh stimulated immediate discussion. Dr. Baumans discussed the pros and cons of enrichment, emphasizing the necessities for taking into account the normal behavior of each species and for evaluating enrichment methods. Dr. Vandenbergh elaborated on this point noting that guidelines must have a positive strategy; they should identify a scientific basis and measure outcome appropriately; and they should be performance based. This combination of requirements poses larger issues in that it is difficult to define what to measure, what the approach should be, and how to interpret the findings. Cortisol, for example, is not the Holy Grail to indicate the extent of animal welfare. Stress and steroid responses have both good and bad effects, depending on circumstance. Dr. Vandenbergh further indicated that guidelines must not be based on subjective measurements; they must garner respect of the scientific community and must have sensitivity to the needs of science. Participants felt that guidelines, and the creation of new guidelines, must encourage and stimulate science. Institutional animal care and use committees, for example, could help facilitate science by filling voids in the knowledge base by encouraging needed studies that are specific to their institutions or needs. Rigid regulations or interpretation of guidelines as such tend to place restrictions on process, thus yielding less science-based information. Primate enrichment guidelines are a good example. Enrichment programs are required, but the institution is left to
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop be creative in implementing an enrichment plan. This situation encourages creative approaches in lieu of standardized and intrusive regulations. Nevertheless, the argument was advanced by some in the group that it may be necessary to establish standards before scientific proof, thereby stimulating research. However, the group also emphasized that in the absence of scientific information, standards should be more general, thereby stimulating research leading to more specific standards. There was divided opinion on this subject. The group discussed sources of funding for developing science-based guidelines. Several options were mentioned, including the American College of Laboratory Animal Medicine Foundation and the Johns Hopkins Center for Alternatives to Animal Testing. The discussion elucidated the reality of laboratory animal welfare. Clear differences exist between Europe and the United States, as well as Asia. The European approach emphasizes detailed regulations that tend to be inflexible, whereas the US and Canadian approaches are based on general guidelines that encourage new approaches and flexibility. The Japanese approach is more cultural and is based on respect of animals and Buddhist philosophy. There is misunderstanding of the US and European policies, and there is misunderstanding of our own respective systems. Shorthand versions of more complex guidelines and regulations tend to be used. Some Europeans stated that there is public pressure for change, and thus they cannot wait for science. This discussion led to considerable response that such an approach is frightening and does not serve anyone well. An additional caveat discussed is that species-specific behaviors on which guidelines and regulations are built are also significant variables. Although basic behavior is retained, domestication inbreeding has adapted animals to the research environment, and there is marked strain-related variation among rodents. Therefore, some participants felt that science-based guidelines should take this adaptation into consideration. Transgenic animals create new challenges. It is dangerous to “lump” rodents, particularly different strains of rodents, together. It was also noted that many things that make animals “happy” are not necessarily good for them. Drug abuse preference or measurements of brain pleasure centers underscore this concept. In summary, more questions arise than answers. What should we measure? Who should measure? Who should fund the work? How should the work be funded? How can the general scientific community be rallied to assist? There are no easy answers. (For consideration of these questions see the discussion following the Point/Counterpoint session on p. 201.)
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Environmental Enrichment for Dogs and Cats Leader: Graham Moore Rapporteur: Janet Gonder The participants began by identifying discussion topics. Topics included enrichment beyond exercise; clarification of the use of structures (do they add or subtract from floor space?); recommendations on socialization; acquisition of animals (e.g., experience and socialization at the vendor); vertical space for dogs; exercise (what, when, how, why); and Council of Europe requirements. Most of the discussion was directed at dogs, but specific issues for cats were noted. The term “enrichment” was considered as a complete package to include housing, structures, toys, socialization (with humans and conspecifics), and exercise. Variability was thought to be of benefit. But what really counts? Some participants posed the thought that human interaction and provision of a cage mate might suffice. Almost everyone agreed that more could be done to socialize/habituate dogs and cats to the laboratory. Early socialization of dogs is critical. Provision of an “enrichment profile” by vendors of purpose-bred dogs and cats was suggested. Of course, such provision would be difficult to achieve with random source animals, as with knowledge of health status, genetics, and so forth. Participants listed what they thought were the key components of an integrated enrichment program. Components include socialization, exercise, pen/cage structures, and other physical enrichment items. Socialization was thought to be critical, particularly in the early development period. This component should include socialization with humans
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop and conspecifics, as well as habituation to the laboratory. The participants generally agreed that single housing should be specifically justified based perhaps on the experimental procedure, genetics or breed variation, specific health or husbandry issues, and individual temperament. Participants did not think the term “exercise” per se to be a particularly helpful guidance. The Council of Europe uses the phrase “physical activity and/or experiencing novel environments.” Participants found the following to be important when considering structures within the enclosure: privacy (may be more important for cats); some control over social interactions; separate areas for different activities; raised platforms; and subdivisions to allow visual stimulation. Other physical enrichment might include items to allow chewing behavior in dogs; items to be used in social interactions with cagemates; items for play (pseudo-predatory behavior) in cats; and utilization of vertical space (the opportunity to climb for cats). In summary, participants believed that institutions should have a written program of care. In addition, the use of laboratory dogs and cats should include integration of multiple components, consider factors that meet both social and behavioral needs of the animals, and take into account procedural or protocol requirements.
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Breakout Session: Assessment of Nonhuman Primate Enrichment—Science Versus Welfare Concerns Leader: Carolyn Crockett Rapporteur: Randall J. Nelson Participants discussed the questions and topics that appear below. What is the scientific basis or peer-reviewed literature that influences or drives the assessment of enrichment for nonhuman primates (NHPs)? What other influences or factors are involved? Where are the gaps in our scientific knowledge? Participants outlined the following benefits of performance standards for assessing environmental enrichment in NHPs: Promote normal behavior: Stimulate a range of normal behaviors, thereby preventing or reducing the development of abnormal behaviors. Reduce abnormal behavior: Redirect activities from abnormal to normal; provide outlets for behaviors that might otherwise be self-directed and possibly injurious. Reduce stress and associated physiological imbalances: Increase the ability of the animal to cope with potentially stressful laboratory experiences. Improve research: By making a healthier research animal (e.g., with normal physiological values), and by reducing subject attrition from development of severe behavior disorders. Other possible benefits.
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Other reasons for providing environmental enrichment for NHPs include: Satisfying public opinion: Providing visible evidence (e.g., enrichment items) that animal welfare concerns with respect to behavioral management are being addressed. Complying with laws: In the United States, complying with the animal welfare regulations requiring environmental enhancement plans adequate to promote psychological well-being. Motivation of workers (technicians): Fortifying the value of the work and its scientific benefit. Other possible reasons. Participants also discussed the assessment of environmental enhancement for nonhuman primates. Discussion topics included use, other benefits, costs, scientific evidence, research protocol constraints, species considerations, and other considerations, as outlined below. Considerations for Enrichment (Scientific evidence supporting use or other benefits vs. professional opinions or anecdotal evidence): Use; preference Percentage of time budget devoted to use of item Choice; simple preference testing Economic models: Elasticity of demand; change in consumption or usage when made more costly Other benefits Facilitating a variety of normal behaviors Reducing abnormal behavior Duration of reduction Generality of reduction (i.e., all or selected undesirable behaviors; e.g., locomotor stereotypy vs. potentially self-injurious behavior) Reducing stress Cortisol Other physiological measures (not yet identified) Behavioral measures of (dis)stress (not yet identified) Other Improving overall health (measures, to be determined) Possible others Costs Monetary cost Time cost: implementation, sanitization, etc. Risk: injury, disease transmission; biosafety concerns for personnel
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Rebound effect; increased cost if enrichment conditions are changed; social and physical Research protocol constraints Good laboratory practice; toxicology Testing; sampling (leaving home cage, perhaps) Infectious disease Species, gender, age considerations, variability Individual differences exist and are noticeable in NHPs Extent to which maladaptive behaviors are caused by environment or inherent in the individual (neurochemical imbalances, organic disease, i.e., need for analgesia in experimental or naturally occurring procedures) Changes in caretakers Other considerations (may affect costs) Documentation of benefit (or lack thereof) Appropriate documentation and person who reviews it Existence versus benefit Determination of intra- versus interinstitutional variability Degree to which literature can suffice, especially with individual NHP variations Communication with others: veterinarians, principal investigators, IACUC members Novelty (i.e., whether variety within this category is necessary to achieve measurable benefit) Frequency of providing this category of enrichment to achieve measurable benefit Other possible factors Minimum Standards (scientifically or anecdotally based) (Context-dependent variables should be considered): Structural enrichment Perches in cages; climbing structures in larger group enclosures NHPs prefer perches in preference studies, but may take a few days to adapt. “A useful furnishing.” Visual barriers: “privacy panels” in cages, barrels, etc., in enclosures Probably reduces contact aggression and allows withdrawal. However, data are scarce, and most are anecdotal. Other possible factors Manipulanda (relatively durable items) “Toys” in cages
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop Mirrors on cages; allow control of environment (viewing of conspecifics) Determination of whether behavioral (experimental) manipulanda constitute enrichment Habituation to items should be avoided and individual variations recognized In the “wild,” youngsters play quite a bit with toys. More individual differences characterize adults. The cost is low; the potential benefit high Simple food treats (not foraging) Produce Other (peanuts, pasta, etc.) Foraging Devices such as puzzle feeders, foraging boards Complex versus simple Frozen treats or complex items for browsing, which also prolong consumption time Floor substrate (bedding or woodchips) in group rooms Special discussion about foraging Should tasks performed for food or drink reward count as “foraging” (if “foraging” experiences specifically required by regulations) Special enrichment items (non-food based) Grooming boards (fleece, turf); paint rollers Destructible: paper, cardboard, wood pieces Other possible items Sensory enrichment (visual, auditory, olfactory) Video, television Murals, colorful shower curtains Music, natural sounds Smells, aromatherapy Windows (to outside, to inside corridor, to other animal rooms) Light level; light cycle Spatial Cage size: Participants did not discuss this topic, but instead reached consensus that cage size should be sufficient to accom-
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The Development of Science-Based Guidelines for Laboratory Animal Care: Proceedings of the November 2003 International Workshop modate all agreed-upon enrichments and to permit normal postural adjustment. Cage level Animals prefer to observe from above, but there is not necessarily a physiological difference to accompany this. Periodic access to larger “activity cage” (frequency, duration) Social Contact Tactile social contact with conspecifics Degrees and type of conspecific contact: visual-only, grooming-contact, pair, small group, typical species-specific group, same-sex, opposite sex, ages, full-time, periodic Age at weaning Age at first single housing Proportion of immature developmental stages spent in single housing Compatible human caregiver versus same species versus “compatible” species; determination of whether human contact can compensate for individual housing Structured human contact (training) versus simple contact (e.g., providing treats). Training is beneficial but not a substitute for conspecific contact. Habituation to caretakers, handlers, experimenters can be beneficial, as can consistency in surroundings. A balance is essential. Discussion points included the observation that some who conduct enrichment programs at their institutions may not be completely trained in the behavior of one or more species for which they are specifying enrichment programs. Enrichment effects are additive, and it is difficult to examine the pieces in isolation. The whole may be greater than the sum of the parts. The consensus of the group was that when the science is not available, expert opinion should be used. With regard to who has the expertise, participants stated that it depends on who has the most experience with the individual NHP in question. The team approach is crucial when establishing the best/good practices to be implemented under the institutional and experimental constraints at any given location. In summary, a cage size should be used that is sufficient to accomplish appropriate enrichment and species-specific behaviors.
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Representative terms from entire chapter: