Index

A

Accreditation of facilities

Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), 9-10

Addictive agents, 109, 114-116, 124

behavior, 115, 142

body weight, 115

withdrawal, 114, 115-116

Agency for Health Care Research and Quality, 8

Aggression, 145-157

behavioral screening tests, 134, 135

behavioral stressors, 143, 144

disease models, 96

distress, 16, 17, 125, 147

genetically modified animals, 66, 132, 133

maternal, 106, 107

pain and distress, 16, 17, 125, 174

pharmacological interventions, 146

predation, 18, 127, 143, 145-147

protocol development, 23

sleep loss, 121

social disruption, 36, 145

American Association for Laboratory Animal Science (AALAS), 8

pain, protocols, 18

American College of Veterinary Behaviorists, 24

American Veterinary Medical Association (AVMA), 24

euthanasia, 26, 27-28, 108

Analgesics

Animal Welfare Regulations (AWRs), 43-44, 108

disease models, 96

nonsteriodal anti-inflammatory drugs (NSAIDS), 22, 43

opioid drugs, 20, 22, 43, 103, 104, 106

perinatal studies, 102, 103, 104-106, 108

prolonged nonsurvival studies, 88-91 (passim)

protocols, 17, 22

preemptive analgesia, 42, 43, 89

regulatory oversight, 11, 17, 43-44

surgery, 11, 17, 20, 35, 42-44, 75, 104

Anatomic studies, 71-73

imaging techniques, 83

Anesthesia, 100-101

Animal Welfare Regulations (AWRs), 43-44

balanced anesthesia regimen, 42. 43. 104

euthanasia, 27-28, 108

Guide for the Care and Use of Laboratory Animals (Guide), 71-72

hypothermia, 105-106



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Index A Accreditation of facilities Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), 9-10 Addictive agents, 109, 114-116, 124 behavior, 115, 142 body weight, 115 withdrawal, 114, 115-116 Agency for Health Care Research and Quality, 8 Aggression, 145-157 behavioral screening tests, 134, 135 behavioral stressors, 143, 144 disease models, 96 distress, 16, 17, 125, 147 genetically modified animals, 66, 132, 133 maternal, 106, 107 pain and distress, 16, 17, 125, 174 pharmacological interventions, 146 predation, 18, 127, 143, 145-147 protocol development, 23 sleep loss, 121 social disruption, 36, 145 American Association for Laboratory Animal Science (AALAS), 8 pain, protocols, 18 American College of Veterinary Behaviorists, 24 American Veterinary Medical Association (AVMA), 24 euthanasia, 26, 27-28, 108 Analgesics Animal Welfare Regulations (AWRs), 43-44, 108 disease models, 96 nonsteriodal anti-inflammatory drugs (NSAIDS), 22, 43 opioid drugs, 20, 22, 43, 103, 104, 106 perinatal studies, 102, 103, 104-106, 108 prolonged nonsurvival studies, 88-91 (passim) protocols, 17, 22 preemptive analgesia, 42, 43, 89 regulatory oversight, 11, 17, 43-44 surgery, 11, 17, 20, 35, 42-44, 75, 104 Anatomic studies, 71-73 imaging techniques, 83 Anesthesia, 100-101 Animal Welfare Regulations (AWRs), 43-44 balanced anesthesia regimen, 42. 43. 104 euthanasia, 27-28, 108 Guide for the Care and Use of Laboratory Animals (Guide), 71-72 hypothermia, 105-106

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imaging studies, 83, 84 inhalation anesthetics, 42, 104, 105, 106, 108 injectable anesthetics, 42, 106 lesions, 98 local anesthesia, 22, 43, 96, 98 multiple major survival surgeries, 32 neurophysiologic recording, 75 professional training, 30, 31 perinatal studies, 102, 103, 104-106, 108 prolonged nonsurvival studies, 88-91 (passim) protocols, 17, 20, 22 regulatory oversight, 11, 17, 43-44 surgery, 11, 17, 32, 37, 41, 42-44, 45, 46, 75, 104 U.S. Government Principles, 42 vocalizations, 106 Animal Care Policies (APHIS/AC Policies), 7-8, 10-11, 17-18 food regulation, 52 prolonged nonsurvival studies, 92 surgeries, 41, 92 Animal husbandry, see Husbandry and nursing care Animal and Plant health Inspection Service, 7 see also Animal Care Policies (APHIS/ AC Policies), 7-8, 10-11, 17-18 Animal Welfare Act, enforcement, 7 Animal Care Panel, 8 Animal Welfare Act (AWA), viii, 3, 7-11 (passim), 17-18, 39, 41 Animal Welfare Regulations (AWRs) anesthetics and analgesics, 43-44 euthanasia, 26-27 fetal surgery, 107-108 food regulation, 52 oversight agencies, general, 7, 8, 9, 12 pain and distress, 17 physical restraint, 49 professional training, 30 prolonged nonsurvival studies, 92 protocols, 13, 17, 39-40 social disruption, 145 surgery, 37-45 (passim), 107-108 Anxiety, 21, 23 behavioral screening of genetically modified animals, 135-136 housing of multiple species, 36-37 physical restraint, 48 Anxiolytics, 23, 43, 90, 135 Appetitive stimuli, 123-125, 130, 138 animal care and use concerns, 126-128 protocols, 126 reasons for, 125-126 terminology, 123-125 Aseptic techniques, 32, 37, 38, 44-45 implants and probes, 73, 76, 80-82, 92-93, 97 lesions, 87 neurophysiologic recording in awake, behaving animals, 72, 73, 75, 78, 79-80, 81-82 professional training, 31 prolonged nonsurvival studies, 76, 89, 92-93 surgery, 37, 38, 40, 44-45, 72, 73, 75, 78, 79 Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC), 9-10 Automated systems, see Computer applications and automated systems Aversive stimuli, 138-139 animal care and use concerns, 52, 126-128 food and fluid regulation, 52 neural injury and diseases, 100, 101 protocol development, 21, 28 reasons for, 125-126 sound, 117 terminology, 123-125 Awake, behaving animals see also Neurophysiologic recording in awake, behaving animals; Physical restraints animal care and use concerns, 76 occupational health and safety concerns, 82 zoonoses, protocols, 29, 46, 85 B Behavior, vii, viii, 1 see also Awake behaving animals; Distress; terms beginning “Behavior...” addictive drugs, 115, 142 disease models, 94-95, 96 distress assessment, protocols, 21, 22 fluid regulation, 50, 51, 57

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food regulation, 50, 51, 53 genetically modified animals, assessment, 63, 66, 67-68 health monitoring, 23-24 heat, 116-117 lesions, 98, 99 mood disorders, 140-142 monitoring of animal health, 23-24, 31, 89, 91, 97-98, 99 pain, 16, 17, 18, 19-20, 22, 43, 89, 99-100, 101, 102-103 pain assessment, protocols, 16, 17, 18, 19-20, 22, 101 pharmaceutical and toxicological studies, 109-110, 114, 115 physical restraint, 47, 48 prolonged nonsurvival studies, 88, 91 postoperative, 35 protocols, 16, 17, 18, 19-20, 22, 23-24 unexpected consequences, 31 Behavioral screening of genetically modified animals, 132-136 aggression, 21-22, 134, 135 animal care and use concerns, 66, 67, 132-134, 136 anxiety tests, 135-136 disease models, 99 general health assessment, 63, 66, 67-68, 86 motivation, 67 motor tests, 134-135, 136 protocols, 136 sensorimotor tests, 134, 136 Behavioral screening of pharmacology/ toxicology studies, 129-132, 133 distress, 21, 22, 127 functional observational battery, 130, 131 motivation, 67 operant test battery, 130 Behavioral stressors, 37, 123-124, 142-149 aggression, 143, 144 humane endpoints, 144 Institutional Animal Care and Use Committees (IACUCs), 144, 149 principal investigator (PI)/veterinarians, 144 protocols, 144 Behavioral studies, 123-149 animal care and use concerns, 126-128 definitions, 123-125 distress, 126, 127 genetically modified animals, 63, 66, 67, 86 learning and memory, 125, 127, 128, 132, 135, 137 motivation, 125, 132, 139 pain, 126, 127-129 pharmaceutical and toxicological studies, 109-110, 142 pilot studies, 149 regulatory concerns, 8-9 Behavioral tasks, 24 Barnes circular platform maze, 128, 136 food and fluid regulation, 50, 59, 139, 140 lesions, 98 mazes, 74, 118, 121, 128, 134, 135, 136 motivation, 9, 49, 50, 51, 55, 57, 59, 60, 119, 127, 128, 131 neurophysiologic recording in awake, behaving animals, 74, 76, 128, 137, 138, 139 restraints, 74, 76 Behavioral training, 30 see also Exercise awake, behaving animals, 74, 75, 76 fluid regulation, 50, 51, 57, 59, 60, 118-119 food regulation, 50, 51, 53, 60, 78, 118-119 motivation, 59, 110, 121; see also Appetitive stimuli; Aversive stimuli neurophysiologic recording, 74, 75, 76, 77-78, 137-140 pain avoidance, 22, 123-125 pharmaceutical and toxicological studies, 110 physical restraint, 48, 77-78 Best practices, 1, 3, 23 Birds, 8 Body weight addictive drugs, 115 fluid regulation, 56, 57 food regulation, 51, 52, 53, 55, 60-61 genetically modified animals, 66, 68 humane endpoints, 24 neurophysiologic recordings, 139-140 pain and, 20, 101 pharmaceutical and toxicological studies, 110, 115 presurgery, 41 unexpected outcomes, monitoring, 33, 34

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C Cats euthanasia, 26 pain indicators, 17, 100 social disruption, 144 zoonoses, 29 Cell/tissue cultures, as alternative to animal subjects, 11 Centers for Disease Control and Prevention, 8 Colonies humane endpoints, 68 monitoring, 33 number of animals required for breeding, 4, 65, 181-187 number of animals required to develop induced mutant, 187-190 Computer applications and automated systems animal care and use concerns, 142 anxiety assessment, 135 exercise devices, 119 neurophysiologic studies, 74 prolonged nonsurvival studies, 91 simulation as alternative to animal use, 11 sleep deprivation, 121, 122 D Department of Agriculture see also Animal and Plant Inspection Service Animal Welfare Act, enforcement, 7, 17-18 colonies, estimating animal numbers needed, 182 surgery, 40 Depression, 21, 31, 140, 141 Porsolt swim test, 141 protocols, 141 tail-suspension test, 141, 141 used to assess distress, 17 Diet and nutrition, see Food regulation Disease models, 94-96 see also Genetically modified animals aggression, 96 animal care and use concerns, 34-35, 96 behavior, 94-95, 96 genetically modified animals, 64 humane endpoints, 24-26, 27, 95 imaging studies, 83 lesions, 97-98 mood disorder, 140-142 occupational health and safety concerns, 95 pain/distress management, 15-16, 94 protocols, 94 stem cell studies, 86 unexpected consequences, 31 Distress, 1, 4 see also Analgesia; Anesthesia; Anxiety; Behavioral stressors; Depression; Pain; Sedatives addictive drugs, withdrawal, 114, 115-116 aggression, 16, 17, 125, 147 assessing distress, 21-22, 134, 135 behavioral signs, 21, 22, 127 behavioral studies, 126, 127 chronic, 21, 26-27 definition, 3, 16 disease models, 95 euthanasia, 26-27, 28 food regulation, 52 humane endpoints, 24-27 hypothermia, 23, 25, 27, 141 lesions, 22, 98 maladaptive behaviors, 22 monitoring, 21-22, 34 multiple major survival surgeries, 32 neurophysiologic recording, 76, 77 noninvasive assessment methods, 21-22 physical restraint, 46-49 (passim), 77 physiologic signs, 21-22 professional training, 31 protocols, 13, 15-28 (passim), 32 regulatory oversight, 10, 16-18 sleep deprivation, 20, 109, 120-122 Dogs euthanasia, 26 pain indicators, 17 socialization, 144 Drugs, see Addictive agents; Pharmacological agents E Education, see Professional training Education and Training in the Care and Use of Laboratory Animals: A Guide for Developing Institutional Programs, 30 Environmental deprivation/stimulation, 120, 147-148 Essentials for Animal Research: A Primer for Research Personnel, 30

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Ethical issues, 3, 10 see also Humane endpoints; Regulatory issues; Standards pain research, 100-101 prolonged nonsurvival studies, 92 3 Rs, 10-11 Euthanasia American Veterinary Medical Association (AVMA), 26, 27-28, 108 anesthetics, 27-28, 108 Animal Welfare Regulations (AWRs), 26-27 AVMA Panel on Euthanasia carbon dioxide, 27, 28, 108 cervical dislocation, 27 decapitation, 27-28, 108 disease models, 95 distress, 26-27, 28 perinatal studies, 102, 108 professional training, 27, 31, 108 protocols, 22, 26-28 sedation, 27-28 Exercise, 109, 118-120 automated systems, 119 fluid regulation, 55 running, 74, 118, 119 swimming, 74, 118-119, 128, 134, 141 Experimental hazards, 29 see also Occupational safety and health F Feces and urine food regulation, 53 genetically modified animals, 61 hazardous wastes, 121 hormonal measures, 22 as hydration indicator, 61 monitoring, 21-22, 139, 140 Fetal studies. 102 anesthesia and analgesia, 103, 104-106 Animal Welfare Regulations (AWRs), 107-108 euthanasia, 102, 108 monitoring, 104, 106-107 pain perception, 103 protocols, 105, 107-108 surgery, 105, 107-108 Fluid regulation, 4, 23, 31, 35, 49-51, 54-61 ad libitum consumption, 55-56, 57, 59 assessing hydration, 54, 55, 58, 59-61 aversive stimuli, 52 behavior, 50, 51, 57 behavioral pain indicators, 17, 20 behavioral tasks, 50, 59, 139, 140 behavioral training, 50, 51, 57, 59, 60, 118-119 body weight, 56, 57 circadian rhythm, 57 designing, 56-57 disease models, 95 exercise, 55 food consumption and, 58 inspection of institutions, 60, 118 Institutional Animal Care and Use Committees (IACUCs), 56, 58, 60 minimum fluid requirements, 55-56 monitoring, 51, 60-61, 139-140 as motivation, 50, 51, 60 pharmaceutical and toxicological studies, 110, 113 physiologic indicators, 54-55, 57, 58 preoperative preparation, 41 protocols, 23, 50, 58 restricted access, 139-140 species/strain differences, 56, 57-58 Food and Drug Administration, 8 Food regulation, 49-54, 117-118 see also Modifying dietary nutrients ad libitum feeding, 51, 52, 53 APHIS/AC Policies, 52 assessing adequacy of nutrition, 51, 52-53, 59-61 behavior, 50, 51, 53 behavioral tasks, 50, 59, 139, 140 behavioral training, 50, 51, 53, 60, 78 body weight, 51, 52, 53, 55, 60-61 circadian rhythm, 53, 54, 57-58 designing, 53 lesions, 99 meal feeding, 53 minimum caloric requirements, 51, 52-53, 117-118 as motivation, 50 pain indicators, 17, 20, 52 pharmaceutical and toxicological studies, 110, 113 physiologic signs, 52, 117-118 postoperative recovery, 35 preoperative preparation, 41 protocols, 50, 51, 118

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restricted feeding, 53, 110, 126, 128, 139-140 soft foods, 34, 35, 99 species/strain differences, 53-54 Funding regulatory considerations, 8 study at hand, 1 G Genetically modified animals, 61-68 aggression, 66, 132, 133 anxiety, 135-136 behavior, 63, 66, 67-68; see also Behavioral screening of genetically modified animals behavioral studies, 63, 66, 67, 86 behavioral tasks, 128 body weight, 66, 68 definitions, 61, 62 depression, 140 disease models, 64 estimating animal numbers to develop a genetically modified animal, 4, 65, 181-190 general health assessment, 66-67 feces and urine, 61 humane endpoints, 26, 67-68 knockin, 62-64 knockout, 14, 62, 63-64, 67, 132, 133-134, 135, 143, 189 monitoring consequences, 31 pain and distress, 15-16, 67-68 protocols, 15-16, 64-67 stem cells, 62-63, 86-93, 133, 141, 189 transgenic animals, 4, 15-16, 61, 62, 64, 134-135, 136, 181-190 Guide for the Care and Use of Laboratory Animals (Guide), viii, 3 agency/oversight bodies using, 8-11 (passim) anatomic studies, 71-72 behavioral studies, 126 euthanasia, 26 fetal studies, 107-108 food regulation, 51 housing of multiple species, 36-37 husbandry, 36 monitoring responsibilities, 35, 36 neonatal studies, 107 neurophysiologic recording, 76, 78 pain and distress, 17, 18, 88-89 physical restraint, 46, 76 pilot studies, 14 prolonged nonsurvival studies, 88-89, 90, 92 protocols, 12, 14, 15, 17, 18, 39, 107-108 sample size, 15 surgical procedures, 37-38, 39, 44, 45, 71-72, 107-108 Guidelines for Research Involving Recombinant DNA Molecules, 87 H Health Research Extension Act (HREA), 8 Historical perspectives, vii-viii protocols, vii, viii regulatory factors, viii, 7-11 Housing, 26-27 colonies, humane endpoints, 68 monitoring, 33 number of animals required, 4, 65, 181-190 distress assessment, protocols, 21 food regulation and, 53 monitoring, 33, 35 multiple species, 36-37 pharmaceutical and toxicological studies, 110 regulatory concerns, 9 space considerations, 37 Humane endpoints see also Euthanasia behavioral stressors, 144 definition, 25, 26 developing, 24-26 dietary nutrient modification, 118 disease models, 23-26, 27, 95 distress, 24-27 exercise, 119 food and fluid regulation, 51 genetically modified animals, 26, 67-68 husbandry and nursing care, 25 neurophysiologic recording in awake, behaving animals, 32, 82 pain, 23-24 physical restraint, 49 Husbandry and nursing care, 34-36 see also Housing dietary nutrients, modification, 118 disease models, 94

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distress assessment, 21 genetically modified animals, 65 humane endpoints, 25 neurophysiologic recordings, 81 pilot studies, 14 post-operative recovery, 38 protocols, 3, 4, 12, 13-14, 21, 35, 36 Hypothermia, 23, 25, 27, 141 distress, 23, 25, 27, 141 perinatal studies, 105 sleep deprivation, 121 surgery, 41, 45-46, 105 I Imaging studies, viii, 71, 74, 83-87, 83-87 animal preparation maintenance during, 83-85 occupational health and safety concerns, 84, 85-86, 87 protocols, 84, 85 techniques available, 83 transportation to and from facilities, 84, 85-86 Implants and probes, 4, 40 asepsis, 73, 76, 80-82, 92-93, 97 drug administration routes, 112 failures, 82 food regulation, 35 housing, 35 imaging studies, 84 lesions, 87 neurophysiologic recording, 74-82 (passim), 138 occupational health and safety concerns, 82 prolonged nonsurvival studies, 89-90, 92-93 protocols, 82 sterilization vs disinfection, 80-81, 93 Indian Health Service, 8 Induced aggression or predation, see Aggression; Predation, induced Inspection of institutions, 14 food/fluid regulation, 60, 118 zoonoses, 29 Institutional Animal Care and Use Committees (IACUCs) anatomic studies, 71-72, 73 appetitive and aversive stimuli, 126, 127, 128-129 behavioral screening, 128, 129, 132, 136 behavioral stressors, 144, 149 colonies, estimating animal numbers needed, 182 depression models, 141 dietary nutrients, modification, 118 exercise, 119 euthanasia, 26, 28 disease models, 35 fetal surgery, 108 fluid regulation, 56, 58, 60 food regulation, 51, 60 genetically modified animals, 64, 67 housing of multiple species, 37 humane endpoints, 25, 26, 118, 119 husbandry and nursing care, 35, 36 monitoring unexpected consequences, 32 lesions, 128 neonatal studies, 106 neurophysiologic recording in awake, behaving animals, 79, 82 oversight agencies and bodies, 7, 8, 9 pain and distress, 17, 67, 100-101, 105; see also “appetitive and aversive...” supra perinatal studies, 104-106 prolonged nonsurvival studies, 89, 92, 93 physical restraint, 47, 49 pilot studies, 14 professional training, 30, 31 protocols, 12, 13, 14, 17, 25, 26, 64, 101, 120 surgery, 37-45 (passim), 108 Institutional Animal Care and Use Guide Book, 17 Institutional officials, 14 Institute for Laboratory Animal Research, 8 Interagency Research Animal Committee, 9 Interdisciplinary teams, see Multi-disciplinary teams International Association for the Study of Pain, 16 Internet regulatory policies, 7, 8, 9 Invasiveness of procedures see also Imaging studies; Implants and probes; Surgery anatomic studies, 71-72 distress assessment, 21, 22 regulatory oversight, 11

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L Laboratory Animal Welfare Act, 7 Learning and memory see also Behavioral tasks; Behavioral training behavioral studies, 125, 127, 128, 132, 135, 137 exercise, 118 general health assessment, 66 lesions, 97 neurophysiologic studies in awake, behaving animals, 137 psychophysical studies, 74 restraints, anxiety, 97 Legislation, ix, 2 see also Regulatory issues Animal Welfare Act (AWA), viii, 3, 7, 9, 10-11, 17-18, 39, 41 Health Research Extension Act (HREA), 8 Laboratory Animal Welfare Act, 7 Public Health Security and Bioterrorsim Act, 116 U.S. Health Research Extension Act of 1985, 8 Lesions, 9, 97-99, 133 anatomic studies, 71 anesthesia, 98 asepsis, 87 disease models, 97-98 housing, 36 monitoring, 32, 98-99 multiple major survival surgeries, 40 pain and distress, 22, 98 protocols, 99 M Memory, see Behavioral training; Learning and memory Methods and Welfare Consideration in Behavioral Research with Animals, 59 Mice behavioral screening, 133, 134-135 food regulation, 53, 54 genetically modified animals, 62-67 (passim) humane endpoints, 25, 67 number of animals required to develop inducted mutant, 187-190 physical restraint, 47 social disruption, 145 transgenic, vii, 62, 134-135 zoonoses, 29 Modified surgical settings, 39, 72, 76, 78, 79 Modifying dietary nutrients, see Food regulation Monitoring of animals, 4 behavior, 23-24, 31, 89, 91, 97-98, 99 behavioral studies, 128-129, 136 body weight, 33, 34 disease models, 94-95, 96 distress, 21-22, 34 exercise, 119 expected and unexpected consequences, 23, 25, 26, 31-34, 66, 87 feces and urine, 21-22, 139, 140 fetal anesthesia, 104, 106-107 food and fluid regulation, 51, 60-61, 139-140 genetically modified animals, 66-68 housing, 33, 35 imaging studies, 84-85 implants, 40 lesions, 32, 98-99 neonatal studies, maternal neglect, 107 neurophysiologic recording in awake, behaving animals, 73-82 (passim), 126, 137-149 pain, 17, 18, 30-31, 34, 101 personnel training, 30-31 pharmaceutical and toxicological studies, 113, 115 physical restraint, 47 pilot studies, 14 postoperative, 35-36, 38, 41, 45-46, 72, 106-107 prolonged nonsurvival studies, 89, 90-92, 93 protocols, 13, 14, 18, 21, 32 recordkeeping, 7, 8, 13, 14, 31, 32-33, 34 euthanasia, 26 exercise, 119 food/fluid regulation, 60 genetically modified animals, 66, 67 neurophysiologic recording, 74-79 (passim), 139-140 physical restraint, 47 sleep deprivation, 122 survival surgery, 41, 45 responsibility for, 35 sleep deprivation, 120, 121-122

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surgery, 35-36, 38, 41, 45-46, 72, 106-107 video techniques, 47, 119, 130 Mood disorder models, 140-142 see also Anxiety; Depression Multi-disciplinary teams behavioral training, 30 husbandry and nursing care, 34 fetal surgery, 108 monitoring of animals, 32, 35 pilot studies, 14 professional training, 30-31 protocols, 12-14 Multiple major survival surgeries, 32, 40-41, 76, 78-79, 97 N National Institutes of Health, 8, 87, 110 Neonatal studies, 102 anesthesia and analgesia, 103, 104-106, 108 cannibalism, 106 euthanasia, 102, 108 hypothermia, 105-106 identification, tagging, tattooing, and toe clipping, 107 maternal neglect, 106-107 maternal separation, 144, 145 pain perception, 99-101 pharmacological/toxicological studies, 103-104 Neuromuscular blocking drugs (NMBD), 88-91 (passim) Neurophysiologic recording in awake, behaving animals, 73-82 (passim), 137-140 animal care and use concerns, 76 asepsis, 72, 73, 75, 78, 79-80, 81-82 behavioral tasks, 74, 76, 137, 138, 139 behavioral training, 74, 75, 76, 137-139 body weight, 139-140 distress, 76, 77 humane endpoints, 32, 82 implants and probes, 74-82 (passim), 138 motivation, 126 physical restraints, 74-81 (passim) veterinarians, 79, 81, 82 NIH Office of Laboratory Animal Welfare, 8 Nonsurvival studies, prolonged, see Prolonged nonsurvival studies Nursing care, see Husbandry and nursing care Nutrition, see Food regulation O Occupational safety and health, 30 behavioral screening, 130 hazardous substances, 82, 116 imaging studies, 84, 85-86, 87 neurophysiologic recording in awake, behaving animals, 82 physical restraint, 46, 47 protocols, 14, 29 stem cell and gene therapy studies, 87 zoonoses, 29, 46, 82, 95 Office of Laboratory Animal Welfare (OLAW), 8 Organ preparation, as alternative to live animals, 11 P Pain, 41 see also Analgesia; Anesthesia; Aversive stimuli; Behavioral stressors; Distress; Euthanasia acceptable levels, 16-17, 18 aggression, 16, 17, 125, 174 animal models, 99-101 assessing pain, 17, 18-21, 24, 99-101 behavioral screening of genetically modified animals, 134 behavioral signs, 16, 17, 18, 19-20, 22, 43, 89, 99-100, 101, 102-103 behavioral studies, 126, 127-129 behavioral training, 22, 123-125 body weight, 20, 101 chronic or persistent, 20, 26-27 decapitation, 27-28 definition, 3, 16, 18 disease models, 15-16, 94 ethical issues, 100-101 fluid regulation, 17, 20 food regulation, 17, 20, 52 genetically modified animals, 15-16, 67-68 Guide for the Care and Use of Laboratory Animals (Guide), 17, 18, 88-89 humane endpoints, 23-26 hypothermia, 23, 25, 27, 141

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Institutional Animal Care and Use Committees (IACUCs), 17, 67, 100-101, 105 lesions, 22, 98 maladaptive behaviors monitoring, 17, 18, 30-31, 34, 101 neurophysiologic recording, 75, 76 perinatal studies, 99-101, 102-104 physical restraint, 49 physiologic measures, 18, 24, 43 professional training on, 31 prolonged nonsurvival studies, 88, 89, 90-91, 92 protocols, 13, 15-25, 26-27, 32, 101 regulatory oversight, 10, 16-18 surgery, 41 threshold, 18. 106, 134 tolerance level, 18, 19, 127, 138-139 unrelieved pain, 23 veterinarians, 23-24 Pain models, 99-101 ethical considerations, 100-101 humane endpoints, 101 persistent pain models, 99, 100, 101 Performance standards, 12 exercise, 119 fetal surgery, 108 prolonged nonsurvival studies, 93 surgery, 38-39, 79 Perinatal studies, 102-108 anaesthesia and analgesia, 102, 103, 104-106, 108 animal care and use, 102 euthanasia, 102, 108 hypothermia, 105 identification, tagging, tattooing, and toe clipping, 107 Institutional Animal Care and Use Committees (IACUCs), 104-106 pain perception, 99-101, 102-104 surgery, postoperative monitoring, cannibalism, and neglect, 106, 107 Pharmacological/toxicological studies, 109-114 see also Behavioral screening of pharmacology/toxicology studies, 129-132 addictive agents, 109, 114-116, 124 aggression, 146 behavior, 109-110, 114, 115 behavioral studies, 109-110, 142 behavioral training, 110 body weight, 110, 115 cannula, 110, 112, 113 chronic drug exposure, 109, 113-116 depression, 140, 141 dose considerations, 22, 111, 113, 114-115 drug administration routes, 112-113, 114 drug-self administration vehicles, 77, 111, 113 fluid/food regulation, 110, 113 food regulation, 110, 113 housing, 110 inhalation, 112-113 implantable pumps, 112 injection, 112, 124 monitoring, 113, 115 occupational health and safety concerns, 116 oral administration, 112, 113 neonatal studies, 103-104 pain and distress, regulatory oversight, 17, 129-131 physical dependence and withdrawal, 114, 115-116 protocols, 113, 115, 118 species/strain differences, 114-115 unexpected consequences, 32 vehicles, 77, 111-112, 114 Physical agents, 116-117 heat, 109, 115, 116-117, 134, 141 light, 50, 53, 109, 116, 117, 135 sound, 36, 109, 116, 117, 123, 136 Physical exercise, see Exercise Physical restraints, see Restraints Physiological indicators, 4 see also Neurophysiologic recording in awake, behaving animals distress, 21-22 euthanasia, 28 fluid regulation, 54-55, 57, 58 food regulation, 52, 117-118 imaging studies, 84-85 lesions, 98-99 pain, 18, 24, 43 physical restraint, distress, 47, 48 postsurgery, 45-46 prolonged nonsurvival studies, 88, 89, 90-91, 92

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Pilot studies, 40 anatomic studies, 71, 72 behavioral, 149 reasons for, 15 protocols, 3, 14-15, 19, 27 sample size, 14, 15, 175 Predation, induced, 18, 127, 143, 145-147 Preparation and Maintenance of Higher Mammals During Neuroscience Experiments, vii, viii, 88, 89, 137 Primates, nonhuman fetal studies, 105 fluid regulation, 50, 55, 56, 118 food regulation, 50, 118 lesions, 97 neurophysiologic recording, 76, 77 pain indicators, 17, 103 physical restraint, 46, 48, 49, 76, 77-78 zoonoses, 29 Principal investigator (PI) behavioral stressors, 144 genetically modified animals, 64 humane endpoints, 26 monitoring, 34 neurophysiologic recording in awake behaving animals, 79 professional training, 30 protocols, 12, 13, 26, 28, 64 surgical procedures, 37, 38 Principles of Humane Experimental Technique, 12 Probes, see Implants and probes Professional training, 2, 30-31 anesthesia, 30, 31 aseptic techniques, 31 distress, 31 euthanasia, 27, 31, 108 genetically modified animals, 65-66 health problem recognition, 33 imaging studies, 84, 85 Institutional Animal Care and Use Committees (IACUCs), 30, 31 monitoring, 30-31 multi-disciplinary, 30-31 neurophysiologic recording in awake, behaving animals, 81 pain, 31 physical restraint, 48 principle investigator (PI), 30 protocols, 14, 27, 29 regulatory concerns, 8-9 zoonoses, 29, 46, 82, 95 Prolonged nonsurvival studies, 3, 4, 75, 88-93 analgesia, 88-91 (passim) anesthesia, 88-91 (passim) APHIS/AC Policies, 92 asepsis, 76, 89, 92-93 automated systems, 91 behavior, 88, 91 implants and probes, 89-90, 92-93 Institutional Animal Care and Use Committees (IACUCs), 89, 92, 93 modified laboratory settings monitoring, 89, 90-92, 93 neuromuscular blocking drugs (NMBD), 88-91 (passim) neurophysiologic recording, 75, 89-92 pain, 88, 89, 90-91, 92 protocols, 89 sterilization vs disinfection, 93 veterinarians, 91, 92, 93 Protocols, 2, 12-29 aggression, 23 analgesics, 17, 22 anesthesia, 17, 20, 22 Animal Welfare Regulations (AWRs), 13, 17, 39-40 appetitive stimuli, 126 aversive stimuli, 21, 28 behavior, 16, 17, 18, 19-20, 21-24 (passim) behavioral stressors, 144 depression, 141 disease models, 94 distress, 13, 15-28 (passim), 32 euthanasia, 22, 26-28 fetal studies, 105, 107-108 fluid regulation, 23, 50, 58 food regulation, 50, 51, 118 genetically modified animals, 15-16, 64-67 Guide for the Care and Use of Laboratory Animals (Guide), 12, 14, 15, 17, 18, 39, 107-108 humane endpoints, 25-26 husbandry and nursing care, 3, 4, 12, 13-14, 21, 35, 36 imaging studies, 84, 85 implants, 82 lesions, 99 monitoring, 13, 14, 18, 21, 32

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multi-disciplinary teams, 12-14 neurologic deficits, 32 occupational health, 14, 29 pharmacological/toxicological studies, 103-104 physical restraint, 46 pilot, 3, 14-15, 19, 27 principle investigator (PI), 12, 13, 26, 28, 64 professional training, 30 prolonged nonsurvival studies, 89 Red Book, vii sample size, 13, 14, 15 surgery, 17, 20, 38, 39, 41-42 veterinarians, 12, 13, 14-15, 23, 26 Public health considerations see also Occupational safety and health imaging studies, 85 transportation of animals, 41-42 Public health Security and Bioterrorsim Act, 116 Public Health Service, 8 Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy) euthanasia, 37 pain and distress, 17 professional training, 30 protocols, 12, 17, 37 regulatory oversight, 8, 9, 10 surgery, 39 R Rabbits pain indicators, 17 physical restraint, 46 surgery, 41 Rats behavioral screening, 130, 131, 132 euthanasia, decapitation, 27 fluid regulation, 56, 57 food regulation, 52, 53-54 genetically modified animals, 62 lesions, 97 pain assessment, 18, 100, 103 physical restraint, 54 regulations concerning, 8 sleep deprivation, 121 zoonoses, 29 Red Book, see Preparation and Maintenance of Higher Mammals During Neuroscience Experiments, vii Regulatory issues, viii, ix, 2, 3, 4, 7-11 see also Animal Care Policies (APHIS/ AC Policies); Animal Welfare Regulations (AWRs); Guide for the Care and Use of Laboratory Animals (Guide); Institutional Animal Care and Use Committees (IACUCs); Legislation; Protocols; Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy); Standards; U.S. Government Principles for the Utilization and Care of Vertebrate Animals Use in Testing, Research, and Training (US Government Principles) agencies/oversight bodies involved, 7-10 analgesics and anesthesia, 11, 17, 43-44 behavioral screening of pharmacology/ toxicology studies, 129-131 behavioral studies, 8-9 behavioral training, 30 distress, 10, 16-18 fetal surgery, 107-108 funding of studies, 8 Internet sites, 7, 8, 9 occupational health and safety, 14 outcome assessment, animal welfare, 9 pain and distress, 10, 16-18 professional training in, 8-9 sample size, 10 sedatives, 11, 17 surgical procedures, 37, 40 veterinarians, 7, 9, 13, 33 Restraints, 46-49 anxiety, 48 behavioral tasks, 74, 76 chairing, 49, 74, 76, 77-78 conditioning animals to , 48 consequences of, 48-49 distress, 46-49 (passim), 77 head-restraint systems, 77, 78-79, 81 humane endpoints, 49 methods, 47-48, 49, 74, 76, 77-78 neurophysiologic recording, 74-81 (passim) observation of animals, 47 prolonged restraint, 46, 48-49

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protocols, 46 reasons for, 46, 73-74 tethering, 76, 77 Rodents see also Mice; Rats anesthetics, 105 addicative drugs, 115 behavioral screening, 130, 135 fetal studies, 105 pain indicators, 17, 103 swimming, 74, 118-119, 128, 134, 141 surgery, 20, 38, 41, 46 transgenic, vii S Sample size determining, 4, 175-180 genetically modified animals, 64-65 pilot studies, 14, 15, 175 protocols, 13, 14, 15 regulatory oversight, 10 Sedatives euthanasia, 27-28 imaging studies, 84 monitoring and, 34 perinatal studies, 103 postsurgical pain, 41 regulatory oversight, 11, 17 Skin condition, 46, 79, 82. 91, 121, 139, 140 hydration indicator, 61 physical restraints, 76 Sleep deprivation, 20, 109, 120-122 Social disruptions, 143-144, 146 aggression, 36, 145 postoperative, 36 predation, 146 restricted social environment, 144 social isolation, 143-144, 148 social separation, 142, 143-144 Special environments, 36-37 Standards, 1 see also Performance standards; Protocols; Regulatory issues anesthetic, neonates, 105 best practices, 1, 3 disease models, occupational health, 85 international, 9-10 Statistical analysis, 15 see also Sample size Stem cell and gene-therapy studies, 62-63, 86-93, 133 animal care and use concerns, 86-87 occupational health and safety, 87 Stress, see Behavioral stressors; Distress Substance Abuse and Mental Health Services Administration, 8 Surgery, 4, 37-46 see also Implants and probes anatomic studies, 71-73 analgesia, 11, 17, 20, 35, 42-44, 75, 104 anesthesia, 11, 17, 32, 37, 41, 42-44, 45, 46, 75, 104 Animal Welfare Regulations (AWRs), 37-45 (passim), 107-108 APHIS/AC Policies, 41, 92 asepsis, 37, 38, 40, 44-45, 72, 73, 75, 78, 79 balanced anesthesia regimens, 42. 43. 104 dedicated surgical facilities, 38, 39, 45, 72, 80, 81, 90 definition, 37-38 fetal studies, 105, 107-108 Guide for the Care and Use of Laboratory Animals (Guide), 37-38, 39, 44, 45, 71-72, 107-108 hypothermia, 41, 45-46, 105 Institutional Animal Care and Use Committees (IACUCs), 37-45 (passim), 108 lesions, 97 major vs minor, 37, 38, 39-40 medical records modified surgical setting/modified laboratory setting, 39, 72, 76, 78, 79 monitoring, 35-36, 38, 41, 45-46, 72, 106-107 multiple major survival surgeries, 32, 40-41, 76, 78-79, 97 neonatal studies, 106 neurophysiologic recording, 73-82 performance standards, 38-39, 79 planning for survival procedures, 41-42 postsurgical recovery, 35-36, 38, 41, 45-46, 72, 106-107 preemptive analgesia, 42, 43, 89 principle investigator (PI), 37, 38 professional training, 30 prolonged nonsurvival studies, 3, 4, 75, 76, 88-93

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protocols, 17, 20, 38, 39, 41-42 rabbits, 41 removal of food, 41 regulatory issues, 37, 40 rodent surgery, 20, 38, 41, 46 survival vs nonsurvival, 37, 38, 41-46 transportation to surgical facilities, 41-42 veterinarians, 37-45 (passim) Survival studies, 4, 71-86 anatomic, 71-73 imaging, viii, 71, 74, 83-87 multiple major survival surgeries, 32, 40-41, 76, 78-79, 97 neurophysiology pain/distress, protocols, 15-16 stem cell and gene-therapy surgical procedures, 37, 40-42 T Thermoregulation, 23, 25, 27, 116-117 see also Hypothermia food regulation 52-53 genetically modified animals, 66, 67 imaging studies, 84-85 neonatal studies, 105, 106 prolonged nonsurvival studies, 92 swimming, 119 3 Rs, 10-11 Tissue cultures, see Cell/tissue cultures Toxicological, see Pharmacological/ toxicological studies Training, see Behavioral training; Professional training Training and supervision of animals, see Behavioral training Transgenic animals, vii, 61, 62, 64, 134-135, 136, 181-190 colonies, number of animals required, 4, 181-190 pain/distress, protocols, 15-16 Transportation to and from facilities imaging studies, 84, 85-86 occupational health and safety, 84, 85-86, 87 public health concerns, 41-42 surgical facilities, 41-42 U Urine, see Feces and urine U.S. Drug Enforcement Administration, 116 U.S. Government Principles for the Utilization and Care of Vertebrate Animals Use in Testing, Research, and Training (US Government Principles), 9, 10, 16-17 anesthesia/analgesia, 42 pain, 138-139 physical restraint, 46 prolonged nonsurvival studies, 88-89 U.S. Health Research Extension Act, 8 V Veterinarians, vii, viii, ix, 1, 4 American Veterinary Medical Association (AVMA), 24, 26 anesthetics and analgesics, 444 appetitive and aversive stimuli, 126 behavioral assessment of animal health, 23-24 behavioral stressors, 144 disease models, 94, 95, 96 euthanasia, 26, 28 fetal surgery, 108 fluid regulation, 56, 58, 139 food restriction, 139 housing of multiple species, 37 husbandry and nursing care, 34 humane endpoints, 26 monitoring, 32-33, 34, 79 neurophysiologic recording in awake, behaving animals, 79, 81, 82 pain and distress management, 23-24 pilot studies, 14 professional training, 31 prolonged nonsurvival studies, 91, 92, 93 protocols, 12, 13, 14-15, 23, 26 regulatory controls, 7, 9, 13, 33 surgical procedures, 37-45 (passim) Vocalizations, 19, 33 anesthesia, 106 genetically modified animals, 66 social disruption, 144

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W Water consumption and regulation, see Fluid regulation Weight, see Body weight World Wide Web, see Internet Z Zoonoses imaging studies, 85 occupational exposures, 29, 46, 82, 95 physical restraint, 46 transportation of animals, public health, 41-42