Refinement and Environmental Enrichment for Primates: Variables

Bibliographyon Refinement and Environmental Enrichment for Primates. Variables


The following reports provide excellentoverviews of the species-typical behavior of wild primates.

Caldecott JO 1986. An Ecological andBehavioral Study of the Pig-tailed macaque. Karger, Basel, Switzerland

Chopra PK, Seth PK, Seth S 1992. Behaviouralprofile of free-ranging rhesus monkeys. Primate Report 32, 75-105

Hall KR 1968. Behaviour and ecologyof the wild patas monkey, Erythrocebus patas, in Uganda. In Primates- Studies in Adaptation and Variability Jay PC (ed), 32-119. Holt,Rinehart and Winston, New York

Hall KRL, DeVore I 1965. Baboon socialbehavior. In Primate Behavior - Field Studies of Monkeys and ApesDeVore I (ed), 53-110. Holt, Rinehart and Winston, New York

Lindburg DG 1971. The rhesus monkeyin North India: an ecological and behavioral study. In PrimateBehavior: Developments in Field and Laboratory Research, Volume2 Rosenblum LA (ed), 1-106. Academic Press, New York, NY

Poirier FE 1970. The Nilgiri langur(Presbytis johnii) of South India. In Primate Behavior: Developmentsin Field and Laboratory Research, Volume 1 Rosenblum LA (ed),251-383. Academic Press, New York

Roonwal ML,Mohnot SM 1977. Primatesof South Asia - Ecology, Sociobiology, and Behavior. Harvard UniversityPress, Cambridge

Schaller GB 1965. The behavior ofthe Mountain Gorilla. In Primate Behavior - Field Studies of Monkeysand Apes DeVore I (ed), 324-367. Holt, Rinehart and Winston, NewYork

Simonds PE 1965. The bonnet macaquein South India. In Primate Behavior - Field Studies of Monkeysand Apes DeVore I (ed), 175-196. Holt, Rinehart and Winston, NewYork

Southwick CH, Beg MA, Siddiqi MR 1965.Rhesus monkeys in North India . In Primate Behavior - Field Studiesof Monkeys and Apes DeVore I (ed), 111-159. Holt, Rinehart andWinston, New York

Teas J, Richie T, Taylor H, SouthwickC 1980. Population patterns and behavioral ecology of rhesus monkeys(Macaca mulatta) in Nepal. In The Macaques: Studies in Ecology,Behavior and Evolution
Lindburgh DG (ed), 247-262. Van Nostrand Reinhold, New York

Van Lawick-Goodall J 1968. A preliminaryreport on expressive movements and communication in the GombeStream chimpanzee. In Primates - Studies in Adaptation and VariabilityJay PC (ed), 313-374. Holt, Rinehart and Winston, New York

Wheatley BP 1999. The Sacred Monkeysof Bali. Waveland Press, Prospect Heights


The following articles describeabnormal behavior patterns commonly shown by captive primates.

Erwin J, Deni R 1979. Strangers ina strange land: Abnormal behavior or abnormal environments? InCaptivity and Behavior Erwin J, Maple T, Mitchell G (eds), 1-28.Van Nostrand Reinhold, New York,

Fittinghoff NA, Lindburg DG, GomberJ, Mitchell G 1974. Consistency and variability in the behaviorof mature, isolation-reared, male rhesus macaques. Primates 15,111-139

Walsh S, Bramblett CA, Alford PL 1982.A vocabulary of abnormal behaviors in restrictively reared chimpanzees.American Journal of Primatology 3, 315-319


(1) Definition
(2) Scientific Principles
(3) Insufficient/Inadequate Space
(4) Understimulation
(5) Single-caging
(6) Premature Weaning
(7) Enforced Restraint

(8) Queue Effect, Sequential Treatment
(9) Unfamiliar Environment
(10) Double-tier Cage Arrangement

(11) Neighbor Effect
(12) Observer Effect,Presence of Personnel
(13) Noise

(1) Definition

An extraneous variable is afactor that is not the object of investigation yet bearsthe potential of changing the research data in uncontrolled ways.

(2) Scientific Principles

American Medical Association 1992.Use of Animals in Biomedical Research - The Challenge and Response- An American Medical Association White Paper. AMA. Groupon Science and Technology, Chicago
"Biomedical experiments are conducted in accordance withthe principles of the scientific method developed by the Frenchphysiologist, Claude Bernard, in 1865. This method establishedtwo requirements for the conduct of a valid experiment: (1) controlof all variables so that only one factor or set of factors ischanged at a time, and (2) the replication of results by otherlaboratories. Unless these requirements are met, an experimentis not considered valid. ... Stressed animals do not make goodresearch subjects."

American Society of Primatologists2000. American Society of Primatologists guidelines for the ethicaltreatment of nonhuman primates. ASP Bulletin 24(4), 4
"We should make use of information on a species naturalhistory to improve management and enrich environments, becausephysical and psychological well-being are essential not only tothe health of the animals but also to the validity of the researchresults."

Animal Welfare Institute 1979. ComfortableQuarters for Laboratory Animals, Seventh Edition. Animal WelfareInstitute, Washington
"Whenever possible, primate conspecifics should be housedtogether in social groups because of their social needs, and theseneeds should not take second place to housing systems designedprimarily for the convenience of animal care technicians. Independentof ethical considerations, to deprive a gregarious animal of itsbasic behavioral, emotional, and social needs is no less detrimentalto the validity of many scientific investigations than deprivationof light, fresh air, food and water."

Bayne K 2005. Environmentalenrichment: Potential for unintended consequences and researchresults. ILAR [Institute for Laboratory Animal Research]Journal 46(2), 129-139
"Although it is unlikely that every possible variablecan be controlled ... more detailed disclosure in journals ...of the living environment of the subject animals .. will allowfor a better comparison of the findings, and contribute to thebroader knowledge base of the effects of enrichment."

Brockway BP, Hassler CR, Hicks N 1993.Minimizing stress during physiological monitoring. In Refinementand Reduction in Animal Testing Niemi SM, Willson JE (eds),56-69. Scientists Center for Animal Welfare, Greenbelt
"Elimination of sources of variability (stress for example)may allow the use of fewer animals giving equally valid results."

Chance MRA, Russell WMS 1997. Thebenefits of giving experimental animals the best possible treatment.In Comfortable Quarters for Laboratory Animals, Eighth EditionReinhardt V (ed), 12-14. Animal Welfare Institute, Washington
"If we use ethological sophistication to provide laboratoryanimals with the very best physical and social environment conditionsfor their well-being, we need to use fewer of them in researchexperiments or routine tests, and our results we be accurate andreliable."

Davis DE, Bennett CL, Berkson G, LangCM, Snyder RL, Pick JR 1973. ILAR Committee on Laboratory AnimalEthology recommendations for a standardized minimum descriptionof animal treatment. ILAR [Institute of Laboratory Animal Resources]News 16(4), 3-4
"It is clear [from this survey] that many investigatorsdo not realize the influence of ... environmental variables [e.g.,housing, handling, temperature, light] on experimental resultsor at least do not adequately describe the environmental historyof the animals used for experimentation."

Ferin M, Carmel PW, Warren MP, HimsworthRL, Frantz AG 1976. Phencyclidine sedation as a technique forhandling rhesus monkeys: Effects on LH, GH, and prolactin secretion.Proceedings of the Society for Experimental Biology and Medicine151, 428-433
"These monkeys, however, are readily alarmed, and it maybe difficult to obtain stable control levels for hormones whichare easily influenced by stress."

Fuchs E 1997. Requirements of biomedicalresearch in terms of housing and husbandry: Neuroscience. PrimateReport 49, 43-46
"Housing conditions are among the parameters which areimportant contributors to the nature, quality, and reproducibilityof research obtained in laboratory animal investigations. ...It is absolutely important that the animals are able to displayas many aspects of their natural behavioural repertoire and confoundingfactors such as abnormal behavior, injuries, diseases, and stressare excluded."

Home Office 1989. Animals(Scientific Procedures) Act 1986. Code of Practice for the Housingand Care of Animals Used in Scientific Procedures. HerMajesty's Stationery Office, London
"Experimental results may be influenced by environmentalconditions. ... To demonstrate any experimental response againstsuch a variable background generates a requirement for greateranimal usage if the result is to be statistically valid."

Lang CM, Vesell ES 1976. Environmentaland genetic factors affecting laboratory animals: impact on biomedicalresearch. Federation Proceedings [Federation of American Societiesfor Experimental Biology. Federation Proceedings] 35, 1123-1124
The survey "suggest that many investigators do not fullyrecognize the influence of environmental and genetic variableson experimental results.... Failure to give an adequate descriptionof these variables makes it difficult, if not impossible, to duplicatean experiment in other laboratories."

Meyerson BJ 1986. Ethology in animalquarters. Acta Physiologica Scandinavica 554 (Supplement),24-31
The requirements for 'carefully controlled conditions' counteractsits fundamental purpose if it results in housing conditions wherethe animals have difficulties in adapting (psychoneuroendocrinechanges which may disturb the experimental results).

National Research Council 1996. Guide for theCare and Use of Laboratory Animals, 7th Edition="http:>. NationalAcademy Press, Washington
"A good management program provides the environment, housing,and care that ... minimizes variations that can affect research.... Animals should be housed with the goal of maximizing species-specificbehaviors and minimizing stress-induced behaviors."

Novak MA, Bayne K 1991. Monkey behaviorand laboratory issues. Laboratory Animal Science 41(4),306-307
"Monkeys are socially complex creatures. When this aspectof their nature is accommodated in research settings, the benefitto science is a less stressed animal that provides meaningfulscientific data."

Öbrink KJ, Rehbinder C 1999.Animal definition: a necessity for the validity of animal experiments?Laboratory Animals 22, 121-130
"'Material and Methods' section mostly reveals an obviousor almost total lack of information about the animals. ... Theanimal definition should not only include species, sex and agebut also ... the environmental conditions to which the animalsare exposed. ... The prerequisites for the use of fewer animalsper project, while still retaining a sufficiently high degreeof accuracy are high levels of reproducibility and precision inthe experimental results. Factors that may affect these will bediscussed in this paper. If a researcher, through carelessnessor ignorance, should use more animals for a project than is necessary,it must be considered unethical. ...Without hesitation, it isa scientific demand that all factors that have not proven to beinsignificant should be checked, controlled or kept constant."

Public Health Service (PHS), U.S.Department of Health and Human Services 1994. Theimportance of animals in biomedical and behavioral research.Laboratory Primate Newsletter 33(4), 12
"Like most people, scientists are concerned about animalwell-being. ... Institutions receiving support from the PublicHealth Service are obliged to adhere to the highest possible standardsfor the humane care and responsible use of laboratory animals.And scientists themselves have adopted the principle: 'Good AnimalCare and Good Science Go Hand in Hand'."

Reinhardt V 1991. Impactof venipuncture on physiological research conducted in consciousmacaques. Journal of Experimental Animal Science 34,212-217
"Despite the fact that venipuncture often is a stressfulevent for research animals, 81% of the [58] studies [assessingstress-sensitive physiological data] did not account for thiscircumstance by providing no information as to how the subjectswere caught and how they were immobilized during venipuncture.... It was concluded that the description of the experimentalanimal's handling prior to and during venipuncture is a methodologicalissue which needs to be clarified in order to account for a dependentpossibly data-biasing variable."

Reinhardt V, Reinhardt A 2000. Bloodcollection procedure of laboratory primates: A neglected variablein biomedical research. Journal of Applied Animal WelfareScience 3, 321-333
"A survey of 75 biomedical articles dealing with stress-dependentblood parameters in caged primates revealed that the conditionsunder which blood collection occurred were in most cases [72%]describedeither not at all or so haphazardly that it would be impossibleto determine if humane handling procedures were used and basicprinciples of scientific methodology applied. These findings wereunexpected because not only is there ample scientific evidencethat stress-sensitive research data are influenced by traditionalblood sampling procedures, but also that those data-biasing effectscan be avoided. If dependent variables of the blood collectionprocedure are not controlled, data variability will increase therebyautomatically also increasing the number of animals needed forstatistical analysis. For ethical and scientific reasons, it wasrecommended that editors of biomedical journals should requirethat authors provide sufficient information of the blood collection- and when applicable also of the sedative injection - procedureto assure that the experiment was done with the smallest numberof animals possible to achieve statistical significance, and thatthe investigation can be replicated reliably in another laboratoryand the research data interpreted with reasonable accuracy."

Reinhardt V, Reinhardt A 2000. Thelower row monkey cage: An overlooked variable in biomedical research.Journal of Applied Animal Welfare Science 3, 141-149
"A survey of 96 primatological articles revealed thatcage location of research monkeys is usually not mentioned (98%),in spite of the fact that the environment of upper- and lower-rowhoused animals markedly differs in terms of light quality, lightintensity and living dimension. Not accounting for these uncontrolledvariables may increase variability of data and, consequently,the number of experimental animals needed to obtain statisticallyacceptable results."

Russell WMS 1997. Shooting the clock:Timeless lessons of the past still guide today's refinement initiatives.Science and Animal Care [WARDS Newsletter] 8(3), 1-2
"Scientifically, we must ensure the validity of researchresults and a stressed animal is not a proper specimen for science."

Russell WMS, Burch RL 1959. ThePrinciples of Humane Experimental Technique="http:>. Methuen &Co., London
"The wages of inhumanity" are "paid in ambiguousor otherwise unsatisfactory experimental results. .. If we can... remove any unwanted source of variance, we reap our rewardat once in smaller residual variance, greater precision, and hencefewer experimental animals."

Schwindaman D 1991. The 1985 animalwelfare act amendments. In Through the Looking Glass. Issuesof Psychological Well-being in Captive Nonhuman Primates NovakMA, Petto AJ (eds), 26-32. American Psychological Association,Washington DC
"It is only common sense, for instance, that an animalwill not respond normally if it is stressed or undernourished.... Because the validity of research results is so dependent onthe health of research animals, the future of science dependson the integrity of scientific methods and the treatment of animalsused in research."

T-W-Fiennes RN 1972. Primates - General.In The UFAW Handbook on the Care and Management of LaboratoryAnimals Fourth Edition UFAW [Universities Federation for AnimalWelfare] (ed), 374-375. Churchill Livingstone, London
"An animal treated unsympathetically is liable to becomeaggressive and uncooperative; furthermore, unless care is takenover its comfort and needs, it is liable to become stressed andthe results of the experiment may be vitiated for this reason."

Veira Y, Brent L 2000. Behavioralintervention program: Enriching the lives of captive nonhumanprimates. American Journal of Primatology 51(Supplement1), 97
"Since its inception, 142 animals have been reported tothe BIP [Behavioral Intervention Program], including chimpanzees,baboons and other monkeys. The most common behaviors reportedwere hair pulling, pacing, rocking and self-aggression."36.6% of the BIP subjects were nursery-reared. It was suggested"that baboons with abnormal behaviors do not cope well withtheir environment [more death of BIP baboons due to managementreasons], are not good candidates for research or breeding purposes,and many [are] eventually euthanized. Our results support theidea that abnormal and stress-related behaviors in nonhuman primateshave a measurable negative impact on research and breeding programeffectiveness."

Warwick C 1990. Important ethologicaland other considerations of the study and maintenance of reptilesin captivity. Applied Animal Behaviour Science 27, 363-366
"The majority of scientists seem to make great effortsto avoid being associated with 'animal welfarist' or to becomeopen to allegations of being somehow 'scientifically soft'. However,awareness of actual and potential stress and distress among animalsin whatever situation should not be regarded as subjective butas a sound scientific base for the study of animals. Whether anobserver maintains a high personal respect of the well-being ofthe individual animal or holds classic concepts of animals asbeing experimental 'models', it should be more widely recognizedthat there is typically a scientific necessity to have animalsat ease with their environments if studies are to remain objective."

Wolfle TL 1996. How different speciesaffect the relationship. In The Human/Research Animal RelationshipKrulisch L, Mayer S, Simmonds RC (eds), 85-91. Scientists Centerfor Animal Welfare, Greenbelt
"It is not an overstatement to say the right technicianinstills qualities in the animals that make them better and morereliable research subjects. Stress, on the other hand, leads toprofound physiological and behavioral changes that increase thevariability of the data and decrease the reliability of the results."

(3) Insufficient/InadequateSpace

Boot R, Leussink AB, Vlug RF 1985.Influence of housing conditions on pregnancy outcome in cynomolgusmonkeys (Macaca fascicularis). Laboratory Animal Science19, 42-47
More successful pregnancies were recorded for females housedindividually in large cages than for females housed in small cages.

Boyce WT, O'Neill-Wagner PL, PriceCS, Haines MC, Suomi SJ 1998. Crowding stress and violent injuriesamong behaviorally inhibited rhesus macaques. Health Psychology17, 285-289
A rhesus group of 36 animals was kept during 6 'warm' monthsin a large outdoor enclosure, during 6 'cold' months confinedin a building. "During the 6-month period of confinementstress, a fivefold acceleration in [medically-attended] injuryincidence was found."

Draper WA, Bernstein IS 1963. Stereotypedbehavior and cage size. Perceptual and Motor Skill 16,231-234
"It was concluded that spatial restriction which doesnot permit 'normal' locomotor behavior, e.g., running, climbing,etc., results in substitute motor expression which frequentlytakes the form of repetitive stereoptyped movement."

Faucheux B, Bertrand M, BourliereF 1978. Some effects of living conditions upon the pattern ofgrowth in stumptail macaque (Macaca arctoides). FoliaPrimatologica 30, 220-236
"Confinement and prolonged lack of physical exercise arevery probably responsible for the reduced weight and size of ourmonkeys bred in laboratory conditions. ... This is apparentlydue to the impaired development and resulting athrophy of themuscles, particularly those of the hind quarters. This athrophywas especially noticeable in lab-bred group II monkeys which havebeen kept in small individual cages [0.8 x 0.8 x 0.6 m] for years..... The ways in which most primates are bred and kept in manyresearch laboratories are obviously far from ideal. Many 'normal'control subjects might well be in fact abnormal both somaticallyand behaviorally."

Kerl J, Rothe H 1996. Influence of cage size and cage equipmenton physiology and behavior of common marmosets (Callithrixjacchus). LaboratoryPrimate Newsletter 35(3), 10-13
"The mean daytime heart rate increased with increasingcage size for the standard cages. This was expected because ofthe increased options for locomotor behavior."

Kitchen AM, Martin AA 1996. The effectsof cage size and complexity on the behaviour of captive commonmarmosets, Callithrix jacchus jacchus. Laboratory Animals30, 317-326
"Stereotyped behaviours, which occurred in the small [furnished]cages, were never exhibited in the large [funished] cages."

Mendoza SP 1999. Squirrel Monkeys.In The UFAW Handbook on the Care and Management of LaboratoryAnimals Seventh Edition UFAW [Universities Federation forAnimal Welfare] (edited by Poole, T. and English, P. ), 591-600.Blackwell Science, Oxford
"The most common form of stereotypic behavior in squirrelmonkeys is an exaggerated head twirling, usually associated withpacing. ... The incidence of the behaviour seems to be more frequentin small cages, and frequent occurrence of this behaviour mayindicate that more space is required."

Paulk HH, Dienske H, Ribbens LG 1977.Abnormal behavior in relation to cage size in rhesus monkeys.Journal of Abnormal Psychology 86, 87-92
"Observations were made of 24 monkeys that were introducedsingly into a [barren] small and a [barren] large test cage. Ina large cage, more normal but less stereotyped locomotion wasshown than in a small cage."

Turnquist J 1985. Passive joint mobilityin patas monkeys: Rehabilitation of caged animals after releaseinto a free-ranging environment. American Journal of PhysicalAnthropology 67, 1-6
Housing in small cages had detrimental effects on joint mobility,which could be reversed by releasing the animals into a free-rangingenvironment.

van Wagenen G 1950. The monkeys. InThe Care and Breeding of Laboratory Animals Farris EJ (ed),1-42. John Wiley, New York
"If sufficient room is not provided, some males will soonshow depression, sitting quietly in the part of the cage whichaffords the best view. For a while this may be interpreted asan adaptation. ... Too often, however, this persistent postureapparently results in a pressure atrophy, bringing on a lower-limbpalsy, the so-called 'cage paralysis'."

Westergaard GC, Izard MK, Drake JH2000. Reproductive performance of rhesus macaques (Macaca mulatta)in two outdoor housing conditions. American Journal ofPrimatology 50, 87-93
"We conclude that, for rhesus macaques, outdoor corralhousing leads to better reproductive performance than does semi-shelteredgang housing, probably as a result of increased individual spaceand relaxation of intense social stressors."

(4) Barren Environment

Bayne K, Dexter SL, Mainzer H, McCullyC, Campbell G, Yamada F 1992. The use of artificial turf as a foraging substratefor individually housed rhesus monkeys (Macaca mulatta). Animal Welfare 1, 39-53
When their cages were not enriched, eight single-caged subjectsexhibited "abnormal behaviors" approximately 37% ofthe time.

Bayne K, Dexter SL, Suomi SJ 1991.Social housing ameliorates behavioral pathologyin Cebus apella. LaboratoryPrimate Newsletter 30(2), 9-12
"No specific enrichment devices were included in the [single-]cages." The seven subjects' mean percentage of occurrenceof "stereotypic behaviors" was 13%.

Bayne K, Mainzer H, Dexter SL, CampbellG, Yamada F, Suomi SJ 1991. The reduction of abnormal behaviorsin individually housed rhesus monkeys (Macaca mulatta) witha foraging/grooming board. American Journal of Primatology23, 23-35
Prior to enrichment, individuals spent on average 25% of theirtime engrossed in abnormal behaviors.

Bayne K, Mainzer H, Dexter SL, CampbellG, Yamada F, Suomi SJ 1991. The reduction of abnormal behaviorsin individually housed rhesus monkeys (Macaca mulatta) witha foraging/grooming board. American Journal of Primatology23, 23-35
Prior to enrichment, individuals spent on average 25% of theirtime engrossed in abnormal behaviors.

Gärtner J 2002. Why every scientistshould care about animal welfare: Abnormal repetitive behaviorand brain function in captive animals. Fourth World Congresson Alternatives and Animal Use in the Life Sciences - Programand Abstracts, 95
"Barren laboratory housing also induces abnormal behaviorsin many species, particularly stereotypies, fur and feather plucking,and self-mutilation. Similar behaviors in human mental disorderare correlated with dysfunction in brain areas that control theselection and sequencing of behavior. Experiments in several captivespecies will be reviewed, showing the same behaviors correlatewith dysfunction in the same brain areas. For instance, in laboratorymice: like stereotypy in autism and schizophrenia, stereotypycorrelates with impairments of basal ganglia function; and likehair pulling in trichotillomania and autism, barbering (hair plucking)correlates with impairments of prefrontal cortex function. Therefore,far from standardizing laboratory animals, barren environmentsmay induce severe brain abnormalities. These abnormalities callthe validity of a wide range of experiments into question. Limitsof current knowledge and pressing research directions will beidentified. In particular, enrichments that prevent these behaviorsmay reduce variability between animals and produce animals thatare better models of normal function. Thus, enrichment may actuallyimprove the standardization of research animals and refine currentanimal models. In short, 'good welfare is good science'."

Kessel AL, Brent L 1996. The effectivenessof cage toys in reducing abnormal behavior in individually housedpigtail macaques. XVIth Congress of the International PrimatologicalSociety/XIXth Conference of the American Society of Primatologists,Madison Abstract No. 519
Prior to the provision of environmental gadgets subjects exhibited"abnormal behavior" 24% of the time.

Lam K, Rupniak NMJ, Iversen SD 1991.Useof a grooming and foraging substrate to reduce cage stereotypiesin macaques. Journal of Medical Primatology 20, 104-109
"Animals exhibited idiosyncratic repertoires of stereotypedbehaviour, including repetitive pacing, swaying circling, bouncing,cage charging, and rocking. These activities occupied on average11% of baseline observation periods" prior to the introductionof the enrichment gadget.

Reinhardt V 1997. Refiningthe traditional housing and handling of laboratory rhesus macaquesimproves scientific methodology. Primate Report 49,93-112
"A monkey housed in an empty cage is literally a behavioralcripple because s/he is chronically deprived of appropriate stimulifor the expression of species-typical behavior patterns. It isdifficult to know objectively if a monkey experiences boredomwhen being kept in an understimulating environment. However, manysuch animals show signs of depression and/or engage in gross behavioraldisorders."

(5) Single-caging

Alexander S, Fontenot MB 2003. Isosexualsocial group formation for environmental enrichment in adult maleMacaca mulatta. AALAS [American Association for LaboratoryAnimal Science] 54th National Meeting Official Program, 141
Thirty-one [38.8%] of a colony of 80, previously single-caged4-10 years old male rhesus macaques had at least one incidenceof self-injurious biting.. During the year prior to group formation,the clinical history of the subjects included a 12.5% incidenceof severe self biting requiring pharmacological intervention andwound care. These animals were treated pharmacologically for 2-11months prior to group formation. All of these cases were removedfrom treatment prior to group formation. No self biting was notedduring a follow-up period of four months after the animals hadbeen transferred to group-housing.

Bellanca RU, Crockett CM 2002. Factorspredicting increased incidence of abnormal behavior in male pigtailedmacaques. American Journal of Primatology 58, 57-69
"Abnormal behavior was unrelated to the subject's housinglocation (biocontainment vs. other facility) or invasiveness ofresearch. Nursery-reared subjects displayed more abnormal behaviorthan mother-reared subjects. Across and within rearing categories,the proportion of the first 48 months of life spent singly housedwas positively related to the amount of abnormal behavior at maturity... Locomotor stereotypy, by far the most frequent form of abnormalbehavior, was positively related to time in single housing butwas unrelated to rearing."

Bellanca RU, Crockett CM 2001. Malepigtailed macaques neonatally separated from mothers for clinicalreasons show increased abnormal behavior as adults. AmericanJournal of Primatology 54(Supplement 1), 52-53
The proportion of the first 48 months of life spent singlyhoused was significantly related to abnormal behavior in maturity.It explained 12.4% of abnormal behavior in mother-reared animals,42.1% in experimental-nursery-reared animals, and 54.5% in clinical-nursery-rearedanimals.

Canadian Council on Animal Care 1984.Non-human primates. In Guide to the Care and Use of ExperimentalAnimals, Volume 2 Canadian Council on Animal Care 163-173.Canadian Council on Animal Care, Ottawa
"Any primate housed alone will probably suffer from socialdeprivation, the stress from which may distort processes, bothphysiological and behavioural."

Chase WK, Marinus LM, Novak MA 2000.A behavioral comparison of male rhesus macaques (Macaca mulatta)in four different housing conditions. American Journal of Primatology51(Supplement 1), 51
Animals in socially restricted housing [single-housing, single-housingwith intermittent social contact] paced significantly more, locomotedsignificantly less and were more aggressive than subjects housedin groups.

Coelho AM, Carey KD, Shade RE 1991.Assessing the effects of social environment on blood pressureand heart rates of baboon. American Journal of Primatology23, 257-267
In the social companion condition, a subject was able to havevisual, tactile, and auditory interactions with his companionthrough the wire mesh walls of the specially designed cages. "Whenanimals were housed with social companions their blood pressureswere consistently lower than when they were either housed individuallyor with social strangers. ... Measurements of cardiovascular physiologyobtained under social housing may more closely model normal physiologythan ... individual housing."

de Waal FBM 1991. The social natureof primates. In Through the Looking Glass. Issues of PsychologicalWell-being in Captive Nonhuman Primates Novak MA, Petto AJ(eds), 67-77. American Psychological Association, Washington
A discussion of the social nature of primates in relationshipto psychological well-being. "Physiological, immunological,and neurological measures collected on isolation-reared (and hencepsychologically deviant) nonhuman primates might not be representative,and therefore might be suboptimal for the development of modelsapplied to the human species. Social housing would avoid thatpossibility. ... Social deprivation should not be considered anymore normal than, say, water or food deprivation."

Gwinn LA 1996. A method for usinga pole housing apparatus to establish compatible pairs among squirrelmonkeys. Contemporary Topics in Laboratory Animal Science35(4), 61
"During nine treatments with an identical test compound,singly housed animals lost significantly more weight on averagethan did pair housed animals."

Jorgensen MJ, Kinsey JH, Novak MA1998. Risk factors for self-injurious behavior in captive rhesusmonkeys (Macaca mulatta). American Journal of Primatology45, 187
"Research has shown that approximately 10% of captive,individually housed monkeys have had some veterinary record ofself-injurious behavior within their life-time." The incidenceof self-biting was 14% [!] in a test colony of 188 male individuallyhoused rhesus macaques. Self-biting animals had spent more time- starting at an earlier age - in single-cages than controls.

Lilly AA, Mehlman PT, Higley J 1999.Trait-like immunological and hematological measures in femalerhesus across varied environmental conditions. American Journalof Primatology 48, 197-223
"Single housing can produce significant, long-term featuresof immunosuppression. ... Long periods of single caging producedsignificant increases in plasma prolactin concentrations, indicativeof stress-induced anxiety. ... The observation that NE [norepinephrine]was significantly decreased during the latter portions of SingleCage Housing may be further, tentative physiological evidencefor the occurrence of depression in these animals. .... As singlecaging continued, an increasing percentage of the animals showedwithdrawal and depression as witnessed by crouching, huddling,and overall inactivity, clearly indicative of an 'inactive' or'despair' phase commonly described."

Line SW, Shively CA, Heise ER, RabinBS, Cohen S 1993. Influence of single caging on cellular immunefunction in female cynomolgus macaques (Macaca fascicularis).American Journal of Primatology 31, 328
Immune responses are affected by housing condition. "Thesefindings suggest that single caging modulates several aspectsof cellular immune function in female cynomolgus monkeys."

Luck CP, Keeble SA 1967. African Monkeys.In The UFAW Handbook on the Care and Management of LaboratoryAnimals Third Edition UFAW [Universities Federation for AnimalWelfare] (ed), 734-742. Churchill Livingstone, London
"If housed in a small cage by itself the vervet may becomelistless and apathetic, although it will survive."

Lutz C, Well A, Novak M 2003. Stereotypicand self-injurious behavior in rhesus macaques: A survey and retrospectiveanalysis of environment and early experience. American Journalof Primatology 60, 1-15
Behavioral assessments of 362 individually housed rhesus monkeyswere collected at the New England Regional Primate Research Center(NERPRC) and combined with colony records. Of the 362 animalssurveyed, 321 [sic] exhibited at least one abnormal behavior (mean:2.3, range: 1-8)."

National Research Council 1998. ThePsychological Well-Being of Nonhuman Primates="http:>. NationalAcademy Press, Washington
"Social interactions are considered to be one of the mostimportant factors influencing the psychological well-being ofmost nonhuman primates. ... The common practice of housing rhesusmonkeys singly calls for special attention. ... Although the causesof self-directed biting are poorly understood, prolonged individualhousing is probably an influential contributing factor."

Novak MA 2003. Self-injurious behavior in rhesus monkeys: Newinsights into its etiology, physiology, and treatment. AmericanJournal of Primatology 59, 3-19
"In our study population, 14% of individually housed monkeys(the vast majority of which are males) have a veterinary recordfor self-inflicted wounding. Wounding is rare, but self-directedbiting is common. SIB can be elicited during aggressive altercationsand may be associated with husbandry events. Some monkeys appearto be more vulnerable to acquiring SIB. This increased vulnerabilityis associated with certain social experiences in the first 2 yearsof life and with exposure to a larger number of moderately stressfulevents as compared to controls."

Novak MA, Kinsey JH, Jorgensen MJ,Hazen TJ 1998. Effects of puzzle feeders on pathological behaviorin individually housed rhesus monkeys. American Journal ofPrimatology 46, 213-227
"Self-injurious behavior (SIB) occurs in about 10% ofindividually housed monkeys. Monkeys with SIB bite their own bodiesfrequently, occasionally inflicting wounds as a result. ... Ofgreat concern is the development of a severe form of abnormalbehavior in which a small percentage of monkeys (about 5-12%)engage in self-inflicted wounding.

Platt DM, Kinsey JH, Jorgenson MJ,Novak MA 1996. Factors affecting the expression of self-injuriousbehavior in rhesus monkeys (Macaca mulatta). XVIth Congressof the International Primatological Society/XIXth Conference ofthe American Society of Primatologists, Abstract No. 768
"Approximately 10% of laboratory housed rhesus monkeysspontaneously develop self-injurious behavior (SIB) such as bitingtheir own bodies with sufficient force to produce tissue damage.... Monkeys with SIB tended to spend a somewhat greater proportionof their lives in individual cages than controls."

Rosenberg DP, Kesel ML 1994. Old-Worldmonkeys. In The Experimental Animal in Biomedical Research.Volume II, Care, Husbandry, and Well-Being - An Overview by SpeciesRollin BE, Kesel ML (eds), 457-483. CPR Press, Boca Raton
"Single or individual caging systems are the basic orstaple housing used for primates. ... Almost all 'hard' scientificdata (as distinguised from 'soft' behavioral data) have been acquiredfrom singly caged primates."

Russell C, Russell WMS 1985. Conflictactivities in monkeys. Social Biology and Human Affairs50, 26-48
Isolated monkeys redirect violence against themselves. They"pinch the same patch of their own skin repeatedly untilit is raw or even bite and tear themselves."

Schapiro SJ, Nehete PN, Perlman JE,Sastry KJ 2000. A comparison of cell-mediated immune responsesin rhesus macaques housed singly, in pairs, or in groups . AppliedAnimal Behaviour Science 68, 67-84
"Since rhesus monkeys live socially in nature, and theimmune responses of singly housed animals differed from thosehoused socially, there is considerable motivation and justificationfor suggesting that the use of singly housed rhesus macaques maycomplicate interpretations of normal immunological responses."

Shively CA, Clarkson TB, Kaplan JR1989. Social deprivation and coronary artery atherosclerosis infemale cynomolgus monkeys. Atherosclerosis 77, 69-76
"We conclude that these findings indicate that singlecage housing promotes coronary artery atherogenesis in these monkeys."

Sokol KA 1993. Commentary: Thinkinglike a monkey - "primatomorphizing" an environmentalenrichment program. Lab Animal 22(5), 40-45
"Solitary confinement is a severe punishment even formonkeys."

Stoinski TS, Czekala N, Lukas KE,Maple TL 2002. Urinary androgen and corticoid levels in captive,male Western lowland gorillas (Gorilla g. gorilla): Age-and social group-related differences. American Journal of Primatology56, 73-87
"Animals housed socially .. had similar corticoid levels,whereas solitary males showed greater corticoid levels than theirsocially-housed counterparts. The increased levels of corticoidsin solitary-housed males suggest this management strategy mightnot be optimal."

Tiefenbacher S, Fahey MA, RowlettJK, Meyer JS, Pouliot AL, Jones BM, Novak MA 2005. The efficacyof diazepam treatment for the management of acute wounding episodesin captive rhesus macaques. Comparative Medicine 55, 387-392
"This study examined the effects of diazepam (Valium)on self-wounding and other abnormal behaviors in eight individuallyhoused male rhesus monkeys (Macaca mulatta). Each monkey's responseto an anxiolytic dose of diazepam (1 mg/kg or greater orally)was compared with the animal's behavior during drug-free periods.When examined across all animals, treatment with diazepam didnot significantly alter wounding frequency or rates of self-directedbiting without wounding. However, closer examination of the datarevealed that four of the animals showed significant decreasesin self-biting and wounding frequency (positive responders, PRgroup), whereas the remaining monkeys showed a trend towards increasedwounding frequency (negative responders, NR group). Subsequentexamination of colony and veterinary records demonstrated thatcompared with NR monkeys, PR monkeys had spent significantly moreyears in individual cage housing and had experienced a greaternumber of minor veterinary procedures."

Yaroshevsky F 1975. Self-mutilationin Soviet prisons. Canadian Psychiatric Association Journal20, 443-446
Isolation "'cages' are so terrible that many prisonersprefer to maim themselves rather than stay there."

(6) PrematureWeaning

Goosen C 1988. Influence of age ofweaning on the behaviour of rhesus monkeys. Primate Eye34, 16-17
"The rather early age of weaning of infants as practisedin the course of the breeding procedure was an important factorin the induction of stereotyped locomotion and of self-directedinfantile behaviour. Both these classes of abnormal behaviourpersist into adulthood."

Reinhardt V 2002. Artificialweaning of Old World monkeys: Benefits and costs. Journalof Applied Animal Welfare Science 5, 149-154
"The perceived benefits of permanent, pre-weaning mother-infantseparation are not supported by scientific findings. ... As longas there is an excessive number of monkeys and insufficient cagespace, there is no ethically legitimate reason for attemptingto enhance the animals' reproductive output, especially when suchmeasures are not proven to be effective but cause unequivocalpsychological distress. ... It is conceivable that maternal-infantseparation for the purpose of artificial weaning flaws primatehusbandry to the extent of increasing - rather than decreasing- the total number of monkeys needed for research. Thus, artificialweaning is not only an avoidable source of distress but it mayalso be an economically unsound management practice."

Warniment A, Brent L 1997. Abnormalbehavior in a captive chimpanzee colony. The Newsletter8(3), 1-3
"The purpose of this study was to link abnormal behaviorsoften expressed by chimpanzees living in captive environmentsto factors related to their care and housing." Individualswho had spent more time with their mothers had less abnormal behavior.

(7) Enforced Restraint

Adams MR, Kaplan JR, Manuck SB, UbersederB, Larkin KT 1988. Persistent sympathetic nervous system arousalassociated with tethering in cynomolgus macaques. LaboratoryAnimal Science 38, 279-282
"Persistent elevation in heart rate associated with tetheringappears to be the result of a persistent influence of the sympatheticnervous system on cardiac function. ... Other organs and systems,e.g., pituitary-gonadal system, also may be affected."

Albrecht ED, Nightingale MS, TownsleyJD 1978. Stress-induced decrease in the serum concentration ofprogesterone in the pregnant baboon. Journal of Endocrinology77, 425-426
Ketamine infusion did not prevent the reduction in the concentrationof progesterone resulting from enforced restraint for blood collection.

Berendt R, Williams TD 1971. The effectof restraint and position upon selected respiratory parametersof two species of Macaca. Laboratory Animal Science21, 502-509
"Restraint significantly affected the tidal volume andrespiration rate."

Bouyer JJ, Dedet L, Debray O, RougenlA 1978. Restraint in primate chair may cause unusual behaviorin baboons: Electrocorticographic correlates and corrective effectsof diazepam. Electroencephalic Clinical Neurophysiology44, 562-567
"The prolonged drowsy-like ECoG [electrocorticogram] andbehaviour may therefore underline a reaction to the 'stress' conditionsbrought on by restraint" in primate chair.

Brockway BP, Hassler CR, Hicks N 1993.Minimizing stress during physiological monitoring. In Refinementand Reduction in Animal Testing Niemi SM, Willson JE (eds),56-69. Scientists Center for Animal Welfare, Greenbelt
"Restraint itself affects the physiological functioningof the animal, measurement error and variability are introducedinto the data."

Bush M, Custer R, Smeller J, BushLM 1977. Physiologic measures of nonhuman primates during physicalrestraint and chemical immobilization. Journal of the AmericanVeterinary Medicine Association (JAVMA) 171, 866-869
"Of 56 physically restrained [during blood collection]primates, 30 (54%) experienced severe metabolic acidosis. .. Theanimals had more rapid respiration and pulse rates, higher rectaltemperatures, and larger base deficit."

Cope FW, Polis BD 1959. Increasedplasma glutamic-oxalacetic transaminase activity in monkeys dueto nonspecific stress effect. Journal of Aviation Medicine30, 90-94
"There can be a rise in SGO-T [serum glutamic-oxalacetictransaminase] in monkeys due to nonspecific stress such a fright,handling or clinical procedures."

Crockett CM, Bowers CL, Sackett GP,Bowden DM 1993. Urinary cortisol responses of longtailed macaquesto five cage sizes, tethering, sedation, and room change. AmericanJournal of Primatology 30, 55-74
"In the tethering study cortisol levels remained somewhatelevated 2-4 weeks after catheterization. After the catheterswere removed, the cortisol levels dropped rapidly although theyremained slightly elevated through the recovery phase."

Fuller. G. B., Hobson WC, Reyes FI,Winter JSD, Faiman C 1984. Influence of restraint and ketamineanesthesia on adrenal steroids, progesterone, and gonadotropinsin rhesus monkeys. Proceedings of the Society for ExperimentalBiology and Medicine (175), 487-490
"Determination of basal circulating hormone levels innonhuman primates presents a problem since handling or restraintof the animal for venipuncture may introduce sufficient stressto change hormonal secretion. .. Each bleeding was made in conscious[female] monkeys after restraining the animal for 2 to 4 min withthe squeeze mechanism of the [home] cage. The arm was manipulatedthrough an opening in the cage mesh and the blood sample taken."Serum cortisol concentrations and adrenal androgens significantlyincreased from the initial bleeding to the second bleeding after30 minutes. "Ketamine does not modify the stress-inducedincrease of either cortisol or adrenal androgens."

Gauquelin-Koch G, Blanquie J-P, FlorenceG, Milhaud C, Gharib C 1996. Hormonal response to restraint inrhesus monkeys. Journal of Medical Primatology 25, 387-396
"These experiments indicate clearly that placement ina restraining chair represents a stimulus of different systemsin monkeys. The responses observed in the present study are predominantlypsychoendocrine responses to unconditioned emotional stimuli associatedwith the chair-restraint situation, despite the fact that theywere acclimated to this system."

Golub MS, Anderson JH 1986. Adaptationof pregnant rhesus monkeys to short-term chair restraint. LaboratoryAnimal Science 36, 507-511
"Heart rate and blood pressure values recorded immediatelyafter the blood sampling [in restraint chair] did not declinewith repetition of this procedure."

Goncharov NP, Taranov AG, AntonichevAV, Gorlushkin VM, Aso T, Ckan SZ, Diczfalusy E 1979. Effectsof stress on the profile of plasma steroids in baboons (Papiohamadyas). Acta Endocrinologica 90, 372-384
Restraint stress affects testosterone, progesterone, and oestradiol.

Goosen DJ, Davies JH, Maree M, DormehlIC 1984. The influence of physical and chemical restraint on thephysiology of the chacma baboon (Papio ursinus). Journalof Medical Primatology 13, 339-351
Restraint leads to leukocytosis.

Hayashi KT, Moberg GP 1987. Influenceof acute stress and the adrenal axis on regulation of LH and testosteronein the male rhesus monkey (Macaca mulatta). AmericanJournal of Primatology 12, 263-273
"Acute restraint stress appears to cause the transientstimulation of LH release. ... While the stress-stimulated releaseof corticosteroids failed to affect the LH response to GnRH administration,it did act directly on the testes to prevent the normal releaseof testosterone."

Ives M, Dack GM 1956. "Alarmreaction" and normal blood picture in Macaca mulatta.Journal of Laboratory Clinical Medicine 47, 723-729
Authors observed an elevated White Blood Cell Count as "alarmreaction" to physical restraint in rhesus monkeys.

Kaplan JR, Adam MR, Bumsted P 1983.Heart rate changes associated with tethering of cynomolgus monkeys.Laboratory Animal Science 38, 493
"The results suggest that some amount of cardiovascular(and perhaps hormonal) disturbance may persist in tethered animals,even if several weeks are allowed for 'habituation'."

Landi MS, Kissinger JT, Campbell SA,Kenney CA, Jenkins EL 1990. The effects of four types of restrainton serum alanine aminotransferase and asparate aminotransferasein the Macaca fascicularis. Journal of the AmericanCollege of Toxicology 9, 517-523
"All methods of [enforced] restraint resulted in elevationin AST [aspartate aminotransferase] and ALT [alanine aminotransferase]over time."

Line SW, Markowitz H, Morgan KN, StrongS 1991. Effect of cage size and environmental enrichment on behavioraland physiological responses of rhesus macaques to the stress ofdaily events. In Through the Looking Glass. Issues of PsychologicalWell-being in Captive Nonhuman Primates Novak MA, Petto AJ(eds), 160-179. American Psychological Association, Washington
"Restraint with the cage-squeeze mechanism and confinementin a transfer box were both associated with significant increasesin plasma cortisol. ... Repeated exposure to brief restraint didnot lead to habituation of the heart-rate response."

Loomis MR, Henrickson RV, AndersonJH 1980. Effects of ketamine hydrochloride on the hemogram ofrhesus monkeys (Macaca mulatta). Laboratory Animal Science30, 851-853
"Restraining a monkey in its cage represents a stressfulsituation which may result in a physiological leukocytosis andhemoconcentration in the sample collected."

Manning PJ, Lehner NDM, Feldner MA,Bullock BC 1969. Selected hematologic, serum chemical, and arterialblood gas characteristics of squirrel monkeys (Saimiri sciureus).Laboratory Animal Care [Laboratory Animal Science] 19,831-837
Catching and restraint procedures resulted in respiratory alkalosisand metabolic acidosis. Sedation reduced, but did not eliminatethis stress response.

Mason JW 1972. Corticosteroid responseto chair restraint in the monkey. American Journal of Physiology222, 1291-1294
"These experiments indicate clearly that placement inthe restraining chair represents a potent stimulus to the pituitary-adrenalcortical system."

Mason JW, Mougey EH 1972. Thyroid(plasma BEI) response to chair restraint in the monkey. PsychosomaticMedicine 34, 441-448
"Study of 14 of these monkeys throughout a longer periodof 8 weeks of chair restraint indicated that ... mean BEI [butanolextractable iodine] levels remained significantly elevated throughthe third week. ... Acute emotional arousal [enforced restraint]elicits stimulation of the pituitary-thyroid system in the rhesusmonkey."

Mason JW, Wool MS, Wherry FE, PenningtonLL, Brady JV, Beer B 1968. Plasma growth hormone response to avoidancein the monkey. Psychosomatic Medicine 30, 760-773
"Several lines of evidence are presented which suggestthat psychological response to the venipuncture procedure ['forciblyrestrained on rubber mattress in order to perform venipuncture']may be a major determinant of 'baseline' variability in growthhormone levels. The liability of this system appears to be suchthat venipuncture effects may occur within the period of a fewminutes required for a single venipuncture."

McNamee GA, Wannemacher RW, DintermanRE, Rozmiarek H, Montrey RD 1984. A surgical procedure and tetheringsystem for chronic blood sampling, infusion, and temperature monitoringin caged nonhuman primates. Laboratory Animal Science 34,303-307
"The stress of chairing the monkeys may result in a significantdecrease in hemoglobin, hematocrit, and lymphocyte concentrationwith an accompanying neutrophilia. In addition, chair-restrainedmonkeys tend to develop lower leg edema and decubital ulcers onlong-term studies."

Morrow-Tesch JL, McGlone JJ, NormanRL 1993. Consequences of restraint stress on natural killer cellactivity, behavior, and hormone levels in rhesus macaques (Macacamulatta). Psychoendocrinology 18, 383-395
Animals were chair restrained and samples taken after 1, 2and 3 hours. "WBC and the percentage of neutrophils increasedduring the restraint period, while the percent lymphocytes andmonocytes decreased. NK [natural killer cell] activity also decreasedover time after restraint whereas plasma cortisol and ß-endorphinlevels increased significantly."

Morton WR, Knitter GH, Smith PM, SusorTG, Schmit K 1987. Alternatives to chronic restraint of nonhumanprimates. Journal of the American Veterinary Medical Association191, 1282-1286
"Despite attention to details of conditioning and dailyassessments of the animals' health status, chronic chair restraintis accompanied by inherent problems such as skin abrasions, necrosisof the ischial callosities, position-dependent edema, inguinalhernia, rectal prolapse, and laryngeal air sacculitis."

Myers BA, Mendoza SP, Cornelius CE1988. Elevation of plasma glucagon levels in response to stressin squirrel monkeys: Comparison of two subspecies (Saimirisciureus boliviensis and Saimiri sciureus sciureus).Journal of Medical Primatology 17, 205-214
Enforced restraint leads to an elevation of plasma glucagonlevels.

Nakamura RK, Coates R, Crawford H,Friedman D 1982. A flexible restraint chair for the cynomolgusmonkey (Macaca fascicularis). Journal of Medical Primatology11, 178-185