Index

A

Abnormal behavior.

See also specific behaviors

arousal reduction hypothesis, 35

clinical signs of distress, 34-35, 103

examples, 32-33

habit hypothesis, 35

observation strategies, 33, 89-90

recognizing, 4, 11, 19, 33-36

research on, 4, 6, 36, 88

as signs of distress, 3, 4, 16, 19, 35, 103

as signs of stress, 2, 3-4, 14, 16, 36

species-specific, 103

stimulation hypothesis, 35

Adrenocorticotropic hormone (ACTH), 29n.1, 36-37

Age, and distress response, 3, 4, 6, 25, 27, 33, 34, 35, 41, 43, 88, 95-96, 105

Aggression, 3, 4, 16, 26, 28, 30, 68-69, 96, 97, 99, 103, 104, 107, 108, 110, 112

Alleviating distress.

See also Euthanasia

decision and response algorithm, 43, 75, 76

experimental design and, 70-71

recommendations, 6

removal of animal from study, 5, 19, 43, 75

team approach, 75-78

treatment modalities, 66, 75-77

American Association for Laboratory Animal Science, 8, 92

American College of Laboratory Animal Medicine, 8, 92

Analgesics, 70, 75

Animal training, 6, 75, 76, 90

Animal welfare

defining, 17-21

descriptors, 18-19

distress and, 17-21, 33, 88

historical and cultural context, 1, 17-19

institutional support, 7, 91

Animal Welfare Act, 1, 10, 13

Animal Welfare Institute, 7, 8, 91, 92

Anthropocentrism, 90

Anthropomorphism, 20, 90

Anxiety-related behavior, 21, 28, 30, 66-67, 79

Anxiolytics, 66, 75, 77

Arousal reduction hypothesis, 35

Assessment of stress and distress

behavioral, 19, 26, 95-100

considerations in, 4, 18

defining distress and, 3, 18, 88

experimental design and, 4, 43

information resources, 100-101

physiological measures, 19-20

process, 43-44, 106-108

sampling procedures, 36, 37-38, 39, 60

team approach, 4, 42, 43, 44

tools for, 88, 95-112



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Index A American Association for Laboratory Animal Science, 8, 92 Abnormal behavior. See also specific American College of Laboratory Animal behaiors Medicine, 8, 92 arousal reduction hypothesis, 35 Analgesics, 70, 75 clinical signs of distress, 34-35, 103 Animal training, 6, 75, 76, 90 examples, 32-33 Animal welfare habit hypothesis, 35 defining, 17-21 observation strategies, 33, 89-90 descriptors, 18-19 recognizing, 4, 11, 19, 33-36 distress and, 17-21, 33, 88 research on, 4, 6, 36, 88 historical and cultural context, 1, 17-19 as signs of distress, 3, 4, 16, 19, 35, 103 institutional support, 7, 91 as signs of stress, 2, 3-4, 14, 16, 36 Animal Welfare Act, 1, 10, 13 species-specific, 103 Animal Welfare Institute, 7, 8, 91, 92 stimulation hypothesis, 35 Anthropocentrism, 90 Adrenocorticotropic hormone (ACTH), 29 Anthropomorphism, 20, 90 n.1, 36-37 Anxiety-related behavior, 21, 28, 30, 66-67, Age, and distress response, 3, 4, 6, 25, 27, 79 33, 34, 35, 41, 43, 88, 95-96, 105 Anxiolytics, 66, 75, 77 Aggression, 3, 4, 16, 26, 28, 30, 68-69, 96, Arousal reduction hypothesis, 35 97, 99, 103, 104, 107, 108, 110, Assessment of stress and distress 112 behavioral, 19, 26, 95-100 Alleviating distress. See also Euthanasia considerations in, 4, 18 decision and response algorithm, 43, 75, defining distress and, 3, 18, 88 76 experimental design and, 4, 43 experimental design and, 70-71 information resources, 100-101 recommendations, 6 physiological measures, 19-20 removal of animal from study, 5, 19, 43, process, 43-44, 106-108 75 sampling procedures, 36, 37-38, 39, 60 team approach, 75-78 team approach, 4, 42, 43, 44 treatment modalities, 66, 75-77 tools for, 88, 95-112 11

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118 INDEX Association for the Assessment and Brambell Committee, 18 Accreditation of Laboratory Animal Buprenorphine, 77 Care International, 1, 10 Autism, 35 C Autonomic nervous system, 4, 28, 39, 40, 41 Avoidance/escape behavior, 20, 36, 96, 99, Cage cleaning, 69 105, 107 Caloric restriction protocols, 34-35 Avoiding/minimizing distress Cardiovascular disease models, 75 in animal care, 5, 64-70 Cats, 68, 102, 103 in animal use, 5, 70-75 Chlorpromazine, 77 in clinical sampling procedures, 36, 37- Coat/hair/fur 38, 39, 43, 70-71 appearance, 4, 27, 28, 34, 105, 107, enrichment, 5, 6, 7, 11, 19, 31, 32-33, 109 35, 63, 64, 66-67, 69, 75, 77, 90, 91, sampling, 37, 38, 56, 70, 71 96 Cognitive deficits, 21, 27, 28, 52 in experimental design, 5, 6, 11-12, 22, Colitis, 39, 61 63, 70-74, 90 Clinical signs of distress. See also Physiology housing, 11, 18, 19, 43, 63, 65-66, 90 alleviating, 77 humane endpoints, 5, 11-12, 34, 63, 71, assessment tools, 102, 104 88, 111 behavioral, 32-33, 34-35 husbandry, 5, 6, 18, 19, 63, 64, 68, 69- identifying and interpreting, 43, 87-88, 70, 75, 90 95, 104 interference with research aims, 63, 64, sampling procedures, 36, 37-38, 39, 43, 67 70-71 minimally or noninvasive technologies, species-specific, 102 5, 39, 74-75 subclinical, 3, 16 pilot studies, 5, 67, 72 Coprophagy, 32 regulatory requirements, 1, 2, 5, 9-11, Corticosteroid-binding globulin, 27 12, 75, 77 Corticosterone, 27, 37 research, 64 Corticotrophin-releasing hormone, 29, 36, sample size determination, 63, 72-74 37, 39, 40 socialization, 5, 11, 19, 63, 68-69, 90 Cortisol, 4, 29 n.1, 37, 38, 70-71 statistical analyses and, 5, 7, 12, 63, 72- Cross fostering, 29-30 74, 91 canaries, 30 team approach, 5, 63 finches, 30 Three Rs, 5, 6, 63, 64, 89, 90 goats, 30 mice, 30 rats, 30 b Cytokines, 42 Bar chewing, 31, 32 Bar circling, 31 D Barbering, excessive, 32 Behavior. See Abnormal behavior; Normal Decision and response algorithm, 43, 75, behavior; specific behaiors 76, 101 assessment, 20 Defensive behavior, 36, 41, 99 phenotyping, 104-105 Definitions Brain animal welfare, 17-21 function, 19 n.4, 21, 29, 31-32, 41 and assessment of distress, 3, 18, 88 physiological response to stress, 39-40, distress, 1, 3, 10, 11, 13-14, 15-17, 22, 41, 87 88 size and structure, 28, 52

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11 INDEX stress, 2, 3, 11, 14-15, 22 performance standards, 4 suffer/suffering, 18 pilot studies, 5, 72 well-being, 3 repeated measures approach, 73 Dendritic anatomy, 32 sample size determination, 22, 72-74, 90 Depression, 16, 18, 21, 27, 28, 79 sequential designs, 74 Distress. See also Assessment of stress and statistical analysis, 12, 70, 72-74, 89, 91 distress; Avoiding/minimizing distress; Exploratory behavior, 27, 28-29, 31, 37, 52, Clinical signs of distress 76, 105 acute, 14, 34, 95 and animal welfare, 17-21, 22, 88 F behavioral signs, 3, 4, 16, 19, 35, 103 chronic, 16 Fear response, 18, 19, 28, 30, 40-41, 96, defining, 1, 3, 10, 11, 13-14, 15-17, 22, 99, 103, 104 88 Feeding and food-related behavior, 3, 16, development of, 14 20, 33, 36, 68, 95, 96, 98 in natural settings, 25 pharmacological treatment, 77 predictors of, 88 g research implications, 19, 21-22, 63, 65, 67, 88 Gastric ulcers, 16, 21, 39, 61 transition to, 3, 15-17, 20 Gender, and distress response, 3, 4, 6, 25, DNA methylation, 30 26, 27, 33, 34, 36, 41, 43, 88, 95-96 Dogs, 31, 32, 66, 68, 69, 100, 102, 103 Genetic variability Dopamine, 32 and distress response, 3, 4, 6, 28-29 high-reactor monkeys, 28 rhesus monkeys, 28 E Genetically engineered phenotypes, 28, 29, 31, 66-67, 88-89, 105 Endocrinological changes, 28-29, 34, 36-38 Genotyping, 70 Endpoints Glucocorticoids, 2, 14-15, 16, 30, 36-38 determining/establishing, 72, 88, 111 Glucocorticosteroids, 36-38 enrichment strategies and, 88 Grooming behavior, 7, 28, 30, 32, 34, 36, humane, 2, 5, 6, 10, 11-12, 34, 63, 71, 91, 96, 98, 99, 104, 105, 109, 112 88, 111 Growth Enrichment activities, 5, 6, 7, 11, 19, 31, maternal environment and, 31 32-33, 35, 63, 64, 66-67, 69, 75, 77, standardized curves, 25 88, 90, 91, 96 stunted, 17 Ethograms, 26, 52, 95-100 Growth hormone, 38, 58 European Union, Directive on the Protection Guinea pig, 102, 103 of Animals Used for Experimental and Other Scientific Purposes, 13-14 Euthanasia, 6, 43, 71, 74, 77, 78, 79, 88, 89 H Experimental protocols and alleviating distress, 5 Habit bypothesis, 35 and assessment of distress, 4, 43 Housing avoiding/minimizing distress through, 5, alleviating distress, 77-78 6, 11-12, 22, 63, 70-74, 90 avoiding/minimizing distress, 11, 18, 19, caloric restriction, 34-35 43, 63, 65-69, 90 control groups, 74, 89 and behavior, 26, 31-33, 35, 99 effect of distress on, 19, 21-22, 63, 65, differential impacts, 3 67, 88 same-sex groups, 31 humans as animal models, 89

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120 INDEX M Humane endpoints. See also Euthanasia and distress predictors, 88 Macaques, 30, 34, 68, 75, 96 and mice, 71, 111 Marmosets, 68, 96, 97-98, 100 avoiding/minimizing distress, 5, 11-12, Maternal behavior/environment, 25, 26, 34, 63, 71,88,111 29-31, 33, 37 clinical signs, 34 α-Melanocyte stimulating hormone [α- determining/establishing, 71, 88, 111 MSH], 38, 58 primates, 34 Memory, 21, 28 statement of task, 2, 10 3-Methoxy-4-hydroxyphenylglycol, 29 n.1 tiered scoring system, 111 Mice Husbandry, 4, 11, 43 behavioral assessment, 88-89, 104, avoiding/minimizing distress, 5, 6, 18, 105-106 19, 63, 64, 68, 69-70, 75, 90 behavioral signs of distress, 26, 32, 66, genetically manipulated animals, 89 77, 103 prior to euthanasia, 77-78 clinical signs of distress, 102 research needs, 89-90 collagen-induced arthritis model, 111 5-Hydroxyindoleacetic acid, 30 cross-fostered, 29-30 Hypertension, 3, 16-17 enrichment, 32, 66-67 Hypothalamic-pituitary-adrenal (HPA) axis housing, 31, 66, 68, 69 activity, 16, 20-21, 27, 29 n.1, 31, humane endpoints, 71, 111 36-37, 38, 40, 68 Huntington’s disease model, 26, 31 husbandry, 89-90 hyperthermia model, 28 I inbred strains, 15, 26, 28, 73, 104 Immunological changes, 3, 4, 14, 16-17, 21, intraspecies differences in response, 15, 31, 34, 37, 41-42, 67 26, 27, 28 Impulse control, impaired, 30 normal behavior, 26, 27, 29, 31, 32 Inflammatory disease models, 75 scoring sheets, 109-110, 111 Institutional Animal Care and Use socialization, 68, 69 Committees, 2, 5, 10, 12, 43, 63, 64, transgenic and knockout models, 28, 29, 75, 79, 89 31, 66-67, 88-89, 105 Interleukin-1, 42 tumor models, 74-75 Mouse Phenome Database, 15 n.1 J N Johns Hopkins Center for Alternatives to Animal Testing, 8, 92 N-methyl D-aspartate-dependent long-term potentiation-like process, 40 National Center for the Replacement, L Refinement and Reduction of Animals in Research (UK), 7-8, 91-92 Learning abilities, 28, 34, 43, 52, 53, 54, 70 National Institutes of Health, 8, 91-92 Leukemia models, 71 Nest building, 31 Light conditions, 65, 78 Neuroendocrine stress resistance, 37 Locomotor activity, 26, 27, 28, 31, 34, 35, Neurological changes, 14, 34. See also 52 Brain Luteinizing hormone, 38, 58 autonomic nervous system, 4, 28, 39, 40, 41, 60 neurotransmitters, 32, 39-41 Neuropeptide Y, 40

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121 INDEX Neurotransmitters, 39-41 Postnatal separation. See Rearing Noise stressors, 65-66, 78 Poultry, 66 Normal behavior Prepulse inhibition behavior, 31-32 age and, 4, 27, 34, 52, 95, 97 Preventing distress. See Alleviating distress; defined, 65 Avoiding/minimizing distress ethograms, 26, 52, 95-100 Primate Enrichment Database, 7, 91 gender and, 4, 26, 27, 33, 34, 95 Primates, nonhuman. See also Macaques; genetic variation, 4, 25, 26, 27, 28-29, Marmosets; Rhesus monkeys; Vervet 34, 52, 95 monkeys housing and, 26, 31-33 alleviating distress in, 76, 77 infant-related, 97 enrichment, 31 identifying, 4, 11, 25, 26-33, 43 ethograms, 100, 102-103 physiological state and, 4, 26, 31, 33, 34 high-reactor monkeys, 28-29 rearing and postnatal separation, 26, humane endpoints, 34 29-31 normal vs. abnormal behavior, 25, 26, tools for assessing, 96-112 28-29, 30-31, 32, 96, 112 transgenic and knockout models, 4, 25, pair testing record, 112 26, 29 rearing environment, 30-31 sample collection methods, 70-71 Prolactin, 2, 4, 14, 38, 58-60 O Oxytocin, 38, 58 R Rabbits, 31, 66, 68, 96, 99, 100, 102, 103, P 104 Rats Pain, 21 clinical signs of distress, 102-103 addressed separately from distress, 1, 9, cross-fostered, 29-30 10, 11 habituation to test environment, 21 assessment, 102-104 housing, 31, 32, 68 chronic neuropathic, 38 husbandry, 69 clinical signs, 104 normal behavior, 27, 30, 31, 32 markers, 38 physiologic effects of stress, 27, 40, 41 sensitivity, 18, 27, 28, 52 shock stimuli response, 16, 40, 41 Peer rearing, 30-31 socialization, 68 Pharmacological interventions, 66, 75, 77 Rearing and postnatal separation, 25, 29-31 Physiology. See also Brain; Clinical signs of Recognition of stress and distress distress; Neurological changes behavioral correlates, 3-4, 11, 19, 26-36; aging and, 27 see also Abnormal behavior; Normal and behavior, 4, 26, 27, 31, 33 behavior endocrinological changes, 28-29, 34, Recommendations, 6-8, 90-92 36-38 Regulatory requirements, 1, 2, 9-11, 75, 77 immunological changes, 3, 4, 14, 16-17, Regurgitation/rumination, 32 21, 31, 34, 37, 41-42, 67 Research on distress. See also Experimental measures of stress and distress, 2, 3, 4, protocols 16, 18, 19-21, 36-42, 56 avoiding/minimizing distress during, 5, subclinical changes, 16-17 79 telemetric monitoring, 39, 61 communication and collaboration in, 8, Pigs, 31, 66, 68 92 Pilot studies, 5, 67, 72 directions for, 6, 87-90 Play behavior, 27, 28, 97, 100 funding, 7-8, 91-92

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122 INDEX T publication of, 7, 91 scope of this study, 1-2, 10-11 Team approach, 4, 5, 42, 43, 44, 63, 75, Restraint of animals, 15, 16, 19, 37, 38, 41- 101 42, 69, 70, 108 Technological innovations, avoiding/ Rhesus monkeys, 25, 28-29 n.1, 32, 75, 77, minimizing distress through, 39, 96, 100 74-75 Telemetric monitoring, 39, 61 Temperature conditions, 66, 77 S Threat response, 33, 41, 96 S6 kinase gene, 29 Three Rs, 5, 6, 63, 64, 89, 90 Sample size determination, 22, 63, 64, 72- Toxicology studies, 21, 67, 71, 72, 74, 75, 90 106-110 Schizophrenia, 35 Training/experience of personnel, 7, 72 Selective serotonin reuptake inhibitors, 77 Tricyclic antidepressants, 77 Self-injurious behavior, 4, 32, 35, 75, 77, 95 Tumor necrosis factor, 42 Sexual behavior, 15, 33, 36, 96, 98, 99 Shock stimuli response, 16, 40, 41 u Social species, 18, 68 Social subordination, 16 United Kingdom, 7-8 Socialization, 5, 6, 11, 19, 28, 33, 42, 63, U.S. Environmental Protection Agency, 8, 68-69, 90 91-92 Statistical analyses, value in minimizing U.S. Government Principles, 9-10, 11, 13, distress, 5, 7, 12, 63, 70, 72-74, 89, 19-20 91 U.S. Public Health Service Policy for the Stereotypies, 4, 6, 21, 26, 32-33, 35, 77, 88, Humane Care and Use of Animals, 95, 96, 105, 106, 107 1,10 Stimulation hypothesis, 35 Stress acute, 16, 41, 42, 67 v assessment of, 4 behavioral signs, 2, 3-4, 14, 16, 36 Vervet monkeys, 77 chronic mild, 16, 21, 27, 41 Veterinarian’s Oath, 18 n.3 definition, 2, 3, 11, 14-15, 22 Vibration, 66 gender differences, 27 Visual acuity, 28, 52, 69 interference in endpoints, 21 Vocalizations, 16, 31, 34, 96, 99, 104, 106 intraspecies differences, 15 physiological effects, 4, 14, 16, 36-42, 87 W response, 2, 4, 13, 14-15, 16, 22, 29 Well-being sensitivity level, 29 and animal welfare, 7, 17, 21, 91 transition to distress, 3, 15-17, 20 and distress, 14, 17 “useful” or “good,” 16, 22 and stress, 2, 14-15, 17 Stressors assessment, 18, 95 defined, 2, 14 definition, 3 environmental, 65-66 in primates, 25 eustress concept, 15 stereotypies, 21 processive, 40 Weight changes, 5, 7, 25, 26, 27, 34-35, 44, systemic, 40 76, 79, 91, 95, 105, 109, 110 Surrogate peer rearing, 30-31 Wisconsin National Primate Center, 112 Sympathoadrenomedullary system activity, 14, 20-21