Bibliography on Refinement and Environmental Enrichment for Primates. Variables

Species-typical Behavior

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

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

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

Hall KR 1968. Behaviour and ecology of 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 social behavior. In Primate Behavior - Field Studies of Monkeys and Apes DeVore I (ed), 53-110. Holt, Rinehart and Winston, New York

Lindburg DG 1971. The rhesus monkey in North India: an ecological and behavioral study. In Primate Behavior: Developments in Field and Laboratory Research, Volume 2 Rosenblum LA (ed), 1-106. Academic Press, New York, NY

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

Roonwal ML,Mohnot SM 1977. Primates of South Asia - Ecology, Sociobiology, and Behavior. Harvard University Press, Cambridge

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

Simonds PE 1965. The bonnet macaque in South India. In Primate Behavior - Field Studies of Monkeys and Apes DeVore I (ed), 175-196. Holt, Rinehart and Winston, New York

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

Teas J, Richie T, Taylor H, Southwick C 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 preliminary report on expressive movements and communication in the Gombe Stream chimpanzee. In Primates - Studies in Adaptation and Variability Jay PC (ed), 313-374. Holt, Rinehart and Winston, New York

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

Abnormal Behavior

The following articles describe abnormal behavior patterns commonly shown by captive primates.

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

Fittinghoff NA, Lindburg DG, Gomber J, Mitchell G 1974. Consistency and variability in the behavior of 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

Extraneous Variables

(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

An extraneous variable is a factor that is not the object of investigation yet bears the 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. Group on Science and Technology, Chicago
"Biomedical experiments are conducted in accordance with the principles of the scientific method developed by the French physiologist, Claude Bernard, in 1865. This method established two requirements for the conduct of a valid experiment: (1) control of all variables so that only one factor or set of factors is changed at a time, and (2) the replication of results by other laboratories. Unless these requirements are met, an experiment is not considered valid. ... Stressed animals do not make good research subjects."

American Society of Primatologists 2000. American Society of Primatologists guidelines for the ethical treatment of nonhuman primates. ASP Bulletin 24(4), 4
"We should make use of information on a species natural history to improve management and enrich environments, because physical and psychological well-being are essential not only to the health of the animals but also to the validity of the research results."

Animal Welfare Institute 1979. Comfortable Quarters for Laboratory Animals, Seventh Edition. Animal Welfare Institute, Washington
"Whenever possible, primate conspecifics should be housed together in social groups because of their social needs, and these needs should not take second place to housing systems designed primarily for the convenience of animal care technicians. Independent of ethical considerations, to deprive a gregarious animal of its basic behavioral, emotional, and social needs is no less detrimental to the validity of many scientific investigations than deprivation of light, fresh air, food and water."

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

Brockway BP, Hassler CR, Hicks N 1993. Minimizing stress during physiological monitoring. In Refinement and 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. The benefits of giving experimental animals the best possible treatment. In Comfortable Quarters for Laboratory Animals, Eighth Edition Reinhardt V (ed), 12-14. Animal Welfare Institute, Washington
"If we use ethological sophistication to provide laboratory animals with the very best physical and social environment conditions for their well-being, we need to use fewer of them in research experiments or routine tests, and our results we be accurate and reliable."

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

Ferin M, Carmel PW, Warren MP, Himsworth RL, Frantz AG 1976. Phencyclidine sedation as a technique for handling rhesus monkeys: Effects on LH, GH, and prolactin secretion. Proceedings of the Society for Experimental Biology and Medicine 151, 428-433
"These monkeys, however, are readily alarmed, and it may be difficult to obtain stable control levels for hormones which are easily influenced by stress."

Fuchs E 1997. Requirements of biomedical research in terms of housing and husbandry: Neuroscience. Primate Report 49, 43-46
"Housing conditions are among the parameters which are important contributors to the nature, quality, and reproducibility of research obtained in laboratory animal investigations. ... It is absolutely important that the animals are able to display as many aspects of their natural behavioural repertoire and confounding factors such as abnormal behavior, injuries, diseases, and stress are excluded."

Home Office 1989. Animals (Scientific Procedures) Act 1986. Code of Practice for the Housing and Care of Animals Used in Scientific Procedures. Her Majesty's Stationery Office, London
"Experimental results may be influenced by environmental conditions. ... To demonstrate any experimental response against such a variable background generates a requirement for greater animal usage if the result is to be statistically valid."

Lang CM, Vesell ES 1976. Environmental and genetic factors affecting laboratory animals: impact on biomedical research. Federation Proceedings [Federation of American Societies for Experimental Biology. Federation Proceedings] 35, 1123-1124
The survey "suggest that many investigators do not fully recognize the influence of environmental and genetic variables on experimental results.... Failure to give an adequate description of these variables makes it difficult, if not impossible, to duplicate an experiment in other laboratories."

Meyerson BJ 1986. Ethology in animal quarters. Acta Physiologica Scandinavica 554 (Supplement), 24-31
The requirements for 'carefully controlled conditions' counteracts its fundamental purpose if it results in housing conditions where the animals have difficulties in adapting (psychoneuroendocrine changes which may disturb the experimental results).

National Research Council 1996. Guide for the Care and Use of Laboratory Animals, 7th Edition. National Academy 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-specific behaviors and minimizing stress-induced behaviors."

Novak MA, Bayne K 1991. Monkey behavior and laboratory issues. Laboratory Animal Science 41(4), 306-307
"Monkeys are socially complex creatures. When this aspect of their nature is accommodated in research settings, the benefit to science is a less stressed animal that provides meaningful scientific 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 obvious or almost total lack of information about the animals. ... The animal definition should not only include species, sex and age but also ... the environmental conditions to which the animals are exposed. ... The prerequisites for the use of fewer animals per project, while still retaining a sufficiently high degree of accuracy are high levels of reproducibility and precision in the experimental results. Factors that may affect these will be discussed in this paper. If a researcher, through carelessness or ignorance, should use more animals for a project than is necessary, it must be considered unethical. ...Without hesitation, it is a scientific demand that all factors that have not proven to be insignificant should be checked, controlled or kept constant."

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

Reinhardt V 1991. Impact of venipuncture on physiological research conducted in conscious macaques. Journal of Experimental Animal Science 34, 212-217
"Despite the fact that venipuncture often is a stressful event for research animals, 81% of the [58] studies [assessing stress-sensitive physiological data] did not account for this circumstance by providing no information as to how the subjects were caught and how they were immobilized during venipuncture. ... It was concluded that the description of the experimental animal's handling prior to and during venipuncture is a methodological issue which needs to be clarified in order to account for a dependent possibly data-biasing variable."

Reinhardt V, Reinhardt A 2000. Blood collection procedure of laboratory primates: A neglected variable in biomedical research. Journal of Applied Animal Welfare Science 3, 321-333
"A survey of 75 biomedical articles dealing with stress-dependent blood parameters in caged primates revealed that the conditions under which blood collection occurred were in most cases [72%]described either not at all or so haphazardly that it would be impossible to determine if humane handling procedures were used and basic principles of scientific methodology applied. These findings were unexpected because not only is there ample scientific evidence that stress-sensitive research data are influenced by traditional blood sampling procedures, but also that those data-biasing effects can be avoided. If dependent variables of the blood collection procedure are not controlled, data variability will increase thereby automatically also increasing the number of animals needed for statistical analysis. For ethical and scientific reasons, it was recommended that editors of biomedical journals should require that authors provide sufficient information of the blood collection - and when applicable also of the sedative injection - procedure to assure that the experiment was done with the smallest number of animals possible to achieve statistical significance, and that the investigation can be replicated reliably in another laboratory and the research data interpreted with reasonable accuracy."

Reinhardt V, Reinhardt A 2000. The lower 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 that cage location of research monkeys is usually not mentioned (98%), in spite of the fact that the environment of upper- and lower-row housed animals markedly differs in terms of light quality, light intensity and living dimension. Not accounting for these uncontrolled variables may increase variability of data and, consequently, the number of experimental animals needed to obtain statistically acceptable 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 research results and a stressed animal is not a proper specimen for science."

Russell WMS, Burch RL 1959. The Principles of Humane Experimental Technique. Methuen & Co., London
"The wages of inhumanity" are "paid in ambiguous or otherwise unsatisfactory experimental results. .. If we can ... remove any unwanted source of variance, we reap our reward at once in smaller residual variance, greater precision, and hence fewer experimental animals."

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

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

Veira Y, Brent L 2000. Behavioral intervention program: Enriching the lives of captive nonhuman primates. American Journal of Primatology 51(Supplement 1), 97
"Since its inception, 142 animals have been reported to the BIP [Behavioral Intervention Program], including chimpanzees, baboons and other monkeys. The most common behaviors reported were 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 with their environment [more death of BIP baboons due to management reasons], are not good candidates for research or breeding purposes, and many [are] eventually euthanized. Our results support the idea that abnormal and stress-related behaviors in nonhuman primates have a measurable negative impact on research and breeding program effectiveness."

Warwick C 1990. Important ethological and other considerations of the study and maintenance of reptiles in captivity. Applied Animal Behaviour Science 27, 363-366
"The majority of scientists seem to make great efforts to avoid being associated with 'animal welfarist' or to become open to allegations of being somehow 'scientifically soft'. However, awareness of actual and potential stress and distress among animals in whatever situation should not be regarded as subjective but as a sound scientific base for the study of animals. Whether an observer maintains a high personal respect of the well-being of the individual animal or holds classic concepts of animals as being experimental 'models', it should be more widely recognized that there is typically a scientific necessity to have animals at ease with their environments if studies are to remain objective."

Wolfle TL 1996. How different species affect the relationship. In The Human/Research Animal Relationship Krulisch L, Mayer S, Simmonds RC (eds), 85-91. Scientists Center for Animal Welfare, Greenbelt
"It is not an overstatement to say the right technician instills qualities in the animals that make them better and more reliable research subjects. Stress, on the other hand, leads to profound physiological and behavioral changes that increase the variability of the data and decrease the reliability of the results."

(3) Insufficient/Inadequate Space

Boot R, Leussink AB, Vlug RF 1985. Influence of housing conditions on pregnancy outcome in cynomolgus monkeys (Macaca fascicularis). Laboratory Animal Science 19, 42-47
More successful pregnancies were recorded for females housed individually in large cages than for females housed in small cages.

Boyce WT, O'Neill-Wagner PL, Price CS, Haines MC, Suomi SJ 1998. Crowding stress and violent injuries among behaviorally inhibited rhesus macaques. Health Psychology 17, 285-289
A rhesus group of 36 animals was kept during 6 'warm' months in a large outdoor enclosure, during 6 'cold' months confined in a building. "During the 6-month period of confinement stress, a fivefold acceleration in [medically-attended] injury incidence was found."

Draper WA, Bernstein IS 1963. Stereotyped behavior and cage size. Perceptual and Motor Skill 16, 231-234
"It was concluded that spatial restriction which does not permit 'normal' locomotor behavior, e.g., running, climbing, etc., results in substitute motor expression which frequently takes the form of repetitive stereoptyped movement."

Faucheux B, Bertrand M, Bourliere F 1978. Some effects of living conditions upon the pattern of growth in stumptail macaque (Macaca arctoides). Folia Primatologica 30, 220-236
"Confinement and prolonged lack of physical exercise are very probably responsible for the reduced weight and size of our monkeys bred in laboratory conditions. ... This is apparently due to the impaired development and resulting athrophy of the muscles, particularly those of the hind quarters. This athrophy was especially noticeable in lab-bred group II monkeys which have been 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 many research laboratories are obviously far from ideal. Many 'normal' control subjects might well be in fact abnormal both somatically and behaviorally."

Kerl J, Rothe H 1996. Influence of cage size and cage equipment on physiology and behavior of common marmosets (Callithrix jacchus). Laboratory Primate Newsletter 35(3), 10-13
"The mean daytime heart rate increased with increasing cage size for the standard cages. This was expected because of the increased options for locomotor behavior."

Kitchen AM, Martin AA 1996. The effects of cage size and complexity on the behaviour of captive common marmosets, Callithrix jacchus jacchus. Laboratory Animals 30, 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 Laboratory Animals Seventh Edition UFAW [Universities Federation for Animal Welfare] (edited by Poole, T. and English, P. ), 591-600. Blackwell Science, Oxford
"The most common form of stereotypic behavior in squirrel monkeys is an exaggerated head twirling, usually associated with pacing. ... The incidence of the behaviour seems to be more frequent in small cages, and frequent occurrence of this behaviour may indicate 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 introduced singly into a [barren] small and a [barren] large test cage. In a large cage, more normal but less stereotyped locomotion was shown than in a small cage."

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

van Wagenen G 1950. The monkeys. In The Care and Breeding of Laboratory Animals Farris EJ (ed), 1-42. John Wiley, New York
"If sufficient room is not provided, some males will soon show depression, sitting quietly in the part of the cage which affords the best view. For a while this may be interpreted as an adaptation. ... Too often, however, this persistent posture apparently results in a pressure atrophy, bringing on a lower-limb palsy, the so-called 'cage paralysis'."

Westergaard GC, Izard MK, Drake JH 2000. Reproductive performance of rhesus macaques (Macaca mulatta) in two outdoor housing conditions. American Journal of Primatology 50, 87-93
"We conclude that, for rhesus macaques, outdoor corral housing leads to better reproductive performance than does semi-sheltered gang housing, probably as a result of increased individual space and relaxation of intense social stressors."

(4) Barren Environment

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

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

Bayne K, Mainzer H, Dexter SL, Campbell G, Yamada F, Suomi SJ 1991. The reduction of abnormal behaviors in individually housed rhesus monkeys (Macaca mulatta) with a foraging/grooming board. American Journal of Primatology 23, 23-35
Prior to enrichment, individuals spent on average 25% of their time engrossed in abnormal behaviors.

Bayne K, Mainzer H, Dexter SL, Campbell G, Yamada F, Suomi SJ 1991. The reduction of abnormal behaviors in individually housed rhesus monkeys (Macaca mulatta) with a foraging/grooming board. American Journal of Primatology 23, 23-35
Prior to enrichment, individuals spent on average 25% of their time engrossed in abnormal behaviors.

Gärtner J 2002. Why every scientist should care about animal welfare: Abnormal repetitive behavior and brain function in captive animals. Fourth World Congress on Alternatives and Animal Use in the Life Sciences - Program and Abstracts, 95
"Barren laboratory housing also induces abnormal behaviors in many species, particularly stereotypies, fur and feather plucking, and self-mutilation. Similar behaviors in human mental disorder are correlated with dysfunction in brain areas that control the selection and sequencing of behavior. Experiments in several captive species will be reviewed, showing the same behaviors correlate with dysfunction in the same brain areas. For instance, in laboratory mice: like stereotypy in autism and schizophrenia, stereotypy correlates with impairments of basal ganglia function; and like hair pulling in trichotillomania and autism, barbering (hair plucking) correlates with impairments of prefrontal cortex function. Therefore, far from standardizing laboratory animals, barren environments may induce severe brain abnormalities. These abnormalities call the validity of a wide range of experiments into question. Limits of current knowledge and pressing research directions will be identified. In particular, enrichments that prevent these behaviors may reduce variability between animals and produce animals that are better models of normal function. Thus, enrichment may actually improve the standardization of research animals and refine current animal models. In short, 'good welfare is good science'."

Kessel AL, Brent L 1996. The effectiveness of cage toys in reducing abnormal behavior in individually housed pigtail macaques. XVIth Congress of the International Primatological Society/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. Use of a grooming and foraging substrate to reduce cage stereotypies in macaques. Journal of Medical Primatology 20, 104-109
"Animals exhibited idiosyncratic repertoires of stereotyped behaviour, including repetitive pacing, swaying circling, bouncing, cage charging, and rocking. These activities occupied on average 11% of baseline observation periods" prior to the introduction of the enrichment gadget.

Reinhardt V 1997. Refining the traditional housing and handling of laboratory rhesus macaques improves scientific methodology. Primate Report 49, 93-112
"A monkey housed in an empty cage is literally a behavioral cripple because s/he is chronically deprived of appropriate stimuli for the expression of species-typical behavior patterns. It is difficult to know objectively if a monkey experiences boredom when being kept in an understimulating environment. However, many such animals show signs of depression and/or engage in gross behavioral disorders."

(5) Single-caging

Alexander S, Fontenot MB 2003. Isosexual social group formation for environmental enrichment in adult male Macaca mulatta. AALAS [American Association for Laboratory Animal Science] 54th National Meeting Official Program, 141
Thirty-one [38.8%] of a colony of 80, previously single-caged 4-10 years old male rhesus macaques had at least one incidence of self-injurious biting.. During the year prior to group formation, the clinical history of the subjects included a 12.5% incidence of severe self biting requiring pharmacological intervention and wound care. These animals were treated pharmacologically for 2-11 months prior to group formation. All of these cases were removed from treatment prior to group formation. No self biting was noted during a follow-up period of four months after the animals had been transferred to group-housing.

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

Bellanca RU, Crockett CM 2001. Male pigtailed macaques neonatally separated from mothers for clinical reasons show increased abnormal behavior as adults. American Journal of Primatology 54(Supplement 1), 52-53
The proportion of the first 48 months of life spent singly housed 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-reared animals.

Canadian Council on Animal Care 1984. Non-human primates. In Guide to the Care and Use of Experimental Animals, Volume 2 Canadian Council on Animal Care 163-173. Canadian Council on Animal Care, Ottawa
"Any primate housed alone will probably suffer from social deprivation, the stress from which may distort processes, both physiological 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 Primatology 51(Supplement 1), 51
Animals in socially restricted housing [single-housing, single-housing with intermittent social contact] paced significantly more, locomoted significantly less and were more aggressive than subjects housed in groups.

Coelho AM, Carey KD, Shade RE 1991. Assessing the effects of social environment on blood pressure and heart rates of baboon. American Journal of Primatology 23, 257-267
In the social companion condition, a subject was able to have visual, tactile, and auditory interactions with his companion through the wire mesh walls of the specially designed cages. "When animals were housed with social companions their blood pressures were consistently lower than when they were either housed individually or with social strangers. ... Measurements of cardiovascular physiology obtained under social housing may more closely model normal physiology than ... individual housing."

de Waal FBM 1991. The social nature of primates. In Through the Looking Glass. Issues of Psychological Well-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 relationship to psychological well-being. "Physiological, immunological, and neurological measures collected on isolation-reared (and hence psychologically deviant) nonhuman primates might not be representative, and therefore might be suboptimal for the development of models applied to the human species. Social housing would avoid that possibility. ... Social deprivation should not be considered any more normal than, say, water or food deprivation."

Gwinn LA 1996. A method for using a pole housing apparatus to establish compatible pairs among squirrel monkeys. Contemporary Topics in Laboratory Animal Science 35(4), 61
"During nine treatments with an identical test compound, singly housed animals lost significantly more weight on average than did pair housed animals."

Jorgensen MJ, Kinsey JH, Novak MA 1998. Risk factors for self-injurious behavior in captive rhesus monkeys (Macaca mulatta). American Journal of Primatology 45, 187
"Research has shown that approximately 10% of captive, individually housed monkeys have had some veterinary record of self-injurious behavior within their life-time." The incidence of self-biting was 14% [!] in a test colony of 188 male individually housed 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 female rhesus across varied environmental conditions. American Journal of Primatology 48, 197-223
"Single housing can produce significant, long-term features of immunosuppression. ... Long periods of single caging produced significant increases in plasma prolactin concentrations, indicative of stress-induced anxiety. ... The observation that NE [norepinephrine] was significantly decreased during the latter portions of Single Cage Housing may be further, tentative physiological evidence for the occurrence of depression in these animals. .... As single caging continued, an increasing percentage of the animals showed withdrawal 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, Rabin BS, Cohen S 1993. Influence of single caging on cellular immune function in female cynomolgus macaques (Macaca fascicularis). American Journal of Primatology 31, 328
Immune responses are affected by housing condition. "These findings suggest that single caging modulates several aspects of cellular immune function in female cynomolgus monkeys."

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

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

National Research Council 1998. The Psychological Well-Being of Nonhuman Primates. National Academy Press, Washington
"Social interactions are considered to be one of the most important factors influencing the psychological well-being of most nonhuman primates. ... The common practice of housing rhesus monkeys singly calls for special attention. ... Although the causes of self-directed biting are poorly understood, prolonged individual housing is probably an influential contributing factor."

Novak MA 2003. Self-injurious behavior in rhesus monkeys: New insights into its etiology, physiology, and treatment. American Journal of Primatology 59, 3-19
"In our study population, 14% of individually housed monkeys (the vast majority of which are males) have a veterinary record for self-inflicted wounding. Wounding is rare, but self-directed biting is common. SIB can be elicited during aggressive altercations and may be associated with husbandry events. Some monkeys appear to be more vulnerable to acquiring SIB. This increased vulnerability is associated with certain social experiences in the first 2 years of life and with exposure to a larger number of moderately stressful events as compared to controls."

Novak MA, Kinsey JH, Jorgensen MJ, Hazen TJ 1998. Effects of puzzle feeders on pathological behavior in individually housed rhesus monkeys. American Journal of Primatology 46, 213-227
"Self-injurious behavior (SIB) occurs in about 10% of individually housed monkeys. Monkeys with SIB bite their own bodies frequently, occasionally inflicting wounds as a result. ... Of great concern is the development of a severe form of abnormal behavior 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-injurious behavior in rhesus monkeys (Macaca mulatta). XVIth Congress of the International Primatological Society/XIXth Conference of the American Society of Primatologists, Abstract No. 768
"Approximately 10% of laboratory housed rhesus monkeys spontaneously develop self-injurious behavior (SIB) such as biting their own bodies with sufficient force to produce tissue damage. ... Monkeys with SIB tended to spend a somewhat greater proportion of their lives in individual cages than controls."

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

Russell C, Russell WMS 1985. Conflict activities in monkeys. Social Biology and Human Affairs 50, 26-48
Isolated monkeys redirect violence against themselves. They "pinch the same patch of their own skin repeatedly until it is raw or even bite and tear themselves."

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

Shively CA, Clarkson TB, Kaplan JR 1989. Social deprivation and coronary artery atherosclerosis in female cynomolgus monkeys. Atherosclerosis 77, 69-76
"We conclude that these findings indicate that single cage housing promotes coronary artery atherogenesis in these monkeys."

Sokol KA 1993. Commentary: Thinking like a monkey - "primatomorphizing" an environmental enrichment program. Lab Animal 22(5), 40-45
"Solitary confinement is a severe punishment even for monkeys."

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 Primatology 56, 73-87
"Animals housed socially .. had similar corticoid levels, whereas solitary males showed greater corticoid levels than their socially-housed counterparts. The increased levels of corticoids in solitary-housed males suggest this management strategy might not be optimal."

Tiefenbacher S, Fahey MA, Rowlett JK, Meyer JS, Pouliot AL, Jones BM, Novak MA 2005. The efficacy of diazepam treatment for the management of acute wounding episodes in 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 individually housed male rhesus monkeys (Macaca mulatta). Each monkey's response to 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 did not significantly alter wounding frequency or rates of self-directed biting without wounding. However, closer examination of the data revealed that four of the animals showed significant decreases in self-biting and wounding frequency (positive responders, PR group), whereas the remaining monkeys showed a trend towards increased wounding frequency (negative responders, NR group). Subsequent examination of colony and veterinary records demonstrated that compared with NR monkeys, PR monkeys had spent significantly more years in individual cage housing and had experienced a greater number of minor veterinary procedures."

Yaroshevsky F 1975. Self-mutilation in Soviet prisons. Canadian Psychiatric Association Journal 20, 443-446
Isolation "'cages' are so terrible that many prisoners prefer to maim themselves rather than stay there."

(6) Premature Weaning

Goosen C 1988. Influence of age of weaning on the behaviour of rhesus monkeys. Primate Eye 34, 16-17
"The rather early age of weaning of infants as practised in the course of the breeding procedure was an important factor in the induction of stereotyped locomotion and of self-directed infantile behaviour. Both these classes of abnormal behaviour persist into adulthood."

Reinhardt V 2002. Artificial weaning of Old World monkeys: Benefits and costs. Journal of Applied Animal Welfare Science 5, 149-154
"The perceived benefits of permanent, pre-weaning mother-infant separation are not supported by scientific findings. ... As long as there is an excessive number of monkeys and insufficient cage space, there is no ethically legitimate reason for attempting to enhance the animals' reproductive output, especially when such measures are not proven to be effective but cause unequivocal psychological distress. ... It is conceivable that maternal-infant separation for the purpose of artificial weaning flaws primate husbandry to the extent of increasing - rather than decreasing - the total number of monkeys needed for research. Thus, artificial weaning is not only an avoidable source of distress but it may also be an economically unsound management practice."

Warniment A, Brent L 1997. Abnormal behavior in a captive chimpanzee colony. The Newsletter 8(3), 1-3
"The purpose of this study was to link abnormal behaviors often expressed by chimpanzees living in captive environments to factors related to their care and housing." Individuals who had spent more time with their mothers had less abnormal behavior.

(7) Enforced Restraint

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

Albrecht ED, Nightingale MS, Townsley JD 1978. Stress-induced decrease in the serum concentration of progesterone in the pregnant baboon. Journal of Endocrinology 77, 425-426
Ketamine infusion did not prevent the reduction in the concentration of progesterone resulting from enforced restraint for blood collection.

Berendt R, Williams TD 1971. The effect of restraint and position upon selected respiratory parameters of two species of Macaca. Laboratory Animal Science 21, 502-509
"Restraint significantly affected the tidal volume and respiration rate."

Bouyer JJ, Dedet L, Debray O, Rougenl A 1978. Restraint in primate chair may cause unusual behavior in baboons: Electrocorticographic correlates and corrective effects of diazepam. Electroencephalic Clinical Neurophysiology 44, 562-567
"The prolonged drowsy-like ECoG [electrocorticogram] and behaviour may therefore underline a reaction to the 'stress' conditions brought on by restraint" in primate chair.

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

Bush M, Custer R, Smeller J, Bush LM 1977. Physiologic measures of nonhuman primates during physical restraint and chemical immobilization. Journal of the American Veterinary Medicine Association (JAVMA) 171, 866-869
"Of 56 physically restrained [during blood collection] primates, 30 (54%) experienced severe metabolic acidosis. .. The animals had more rapid respiration and pulse rates, higher rectal temperatures, and larger base deficit."

Cope FW, Polis BD 1959. Increased plasma glutamic-oxalacetic transaminase activity in monkeys due to nonspecific stress effect. Journal of Aviation Medicine 30, 90-94
"There can be a rise in SGO-T [serum glutamic-oxalacetic transaminase] 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 macaques to five cage sizes, tethering, sedation, and room change. American Journal of Primatology 30, 55-74
"In the tethering study cortisol levels remained somewhat elevated 2-4 weeks after catheterization. After the catheters were removed, the cortisol levels dropped rapidly although they remained slightly elevated through the recovery phase."

Fuller. G. B., Hobson WC, Reyes FI, Winter JSD, Faiman C 1984. Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys. Proceedings of the Society for Experimental Biology and Medicine (175), 487-490
"Determination of basal circulating hormone levels in nonhuman primates presents a problem since handling or restraint of the animal for venipuncture may introduce sufficient stress to change hormonal secretion. .. Each bleeding was made in conscious [female] monkeys after restraining the animal for 2 to 4 min with the squeeze mechanism of the [home] cage. The arm was manipulated through an opening in the cage mesh and the blood sample taken." Serum cortisol concentrations and adrenal androgens significantly increased from the initial bleeding to the second bleeding after 30 minutes. "Ketamine does not modify the stress-induced increase of either cortisol or adrenal androgens."

Gauquelin-Koch G, Blanquie J-P, Florence G, Milhaud C, Gharib C 1996. Hormonal response to restraint in rhesus monkeys. Journal of Medical Primatology 25, 387-396
"These experiments indicate clearly that placement in a restraining chair represents a stimulus of different systems in monkeys. The responses observed in the present study are predominantly psychoendocrine responses to unconditioned emotional stimuli associated with the chair-restraint situation, despite the fact that they were acclimated to this system."

Golub MS, Anderson JH 1986. Adaptation of pregnant rhesus monkeys to short-term chair restraint. Laboratory Animal Science 36, 507-511
"Heart rate and blood pressure values recorded immediately after the blood sampling [in restraint chair] did not decline with repetition of this procedure."

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

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

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

Ives M, Dack GM 1956. "Alarm reaction" and normal blood picture in Macaca mulatta. Journal of Laboratory Clinical Medicine 47, 723-729
Authors observed an elevated White Blood Cell Count as "alarm reaction" 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 restraint on serum alanine aminotransferase and asparate aminotransferase in the Macaca fascicularis. Journal of the American College of Toxicology 9, 517-523
"All methods of [enforced] restraint resulted in elevation in AST [aspartate aminotransferase] and ALT [alanine aminotransferase] over time."

Line SW, Markowitz H, Morgan KN, Strong S 1991. Effect of cage size and environmental enrichment on behavioral and physiological responses of rhesus macaques to the stress of daily events. In Through the Looking Glass. Issues of Psychological Well-being in Captive Nonhuman Primates Novak MA, Petto AJ (eds), 160-179. American Psychological Association, Washington
"Restraint with the cage-squeeze mechanism and confinement in a transfer box were both associated with significant increases in plasma cortisol. ... Repeated exposure to brief restraint did not lead to habituation of the heart-rate response."

Loomis MR, Henrickson RV, Anderson JH 1980. Effects of ketamine hydrochloride on the hemogram of rhesus monkeys (Macaca mulatta). Laboratory Animal Science 30, 851-853
"Restraining a monkey in its cage represents a stressful situation which may result in a physiological leukocytosis and hemoconcentration in the sample collected."

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

Mason JW 1972. Corticosteroid response to chair restraint in the monkey. American Journal of Physiology 222, 1291-1294
"These experiments indicate clearly that placement in the restraining chair represents a potent stimulus to the pituitary-adrenal cortical system."

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

Mason JW, Wool MS, Wherry FE, Pennington LL, Brady JV, Beer B 1968. Plasma growth hormone response to avoidance in the monkey. Psychosomatic Medicine 30, 760-773
"Several lines of evidence are presented which suggest that psychological response to the venipuncture procedure ['forcibly restrained on rubber mattress in order to perform venipuncture'] may be a major determinant of 'baseline' variability in growth hormone levels. The liability of this system appears to be such that venipuncture effects may occur within the period of a few minutes required for a single venipuncture."

McNamee GA, Wannemacher RW, Dinterman RE, Rozmiarek H, Montrey RD 1984. A surgical procedure and tethering system for chronic blood sampling, infusion, and temperature monitoring in caged nonhuman primates. Laboratory Animal Science 34, 303-307
"The stress of chairing the monkeys may result in a significant decrease in hemoglobin, hematocrit, and lymphocyte concentration with an accompanying neutrophilia. In addition, chair-restrained monkeys tend to develop lower leg edema and decubital ulcers on long-term studies."

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

Morton WR, Knitter GH, Smith PM, Susor TG, Schmit K 1987. Alternatives to chronic restraint of nonhuman primates. Journal of the American Veterinary Medical Association 191, 1282-1286
"Despite attention to details of conditioning and daily assessments of the animals' health status, chronic chair restraint is accompanied by inherent problems such as skin abrasions, necrosis of the ischial callosities, position-dependent edema, inguinal hernia, rectal prolapse, and laryngeal air sacculitis."

Myers BA, Mendoza SP, Cornelius CE 1988. Elevation of plasma glucagon levels in response to stress in squirrel monkeys: Comparison of two subspecies (Saimiri sciureus boliviensis and Saimiri sciureus sciureus). Journal of Medical Primatology 17, 205-214
Enforced restraint leads to an elevation of plasma glucagon levels.

Nakamura RK, Coates R, Crawford H, Friedman D 1982. A flexible restraint chair for the cynomolgus monkey (Macaca fascicularis). Journal of Medical Primatology 11, 178-185
"There is a general consensus that restraint chairs should be used only where necessary, since they inherently cause monkeys physical and emotional stress." Authors found "that the animals showed restless sleeping patterns which persisted despite our attempts to adapt the animals to the chairs slowly. It was soon evident that the restlessness resulted from the rapid development of chafing at the neck, a breakdown of tissue in the ischial pads, and lesions at the base of the tail."

Norman RL, McGlone J, Smith CJ 1994. Restraint inhibits luteinizing hormone secretion in the follicular phase of the menstrual cycle in rhesus macaques. Biology of Reproduction 50, 16-26
Chair restraint affects LH and ACTH in rhesus macaques.

Norman RL, Smith CJ 1992. Restraint inhibits luteinizing hormone and testosterone secretion in intact male rhesus macaques: Effects of concurrent naloxone administration. Neuroendocrinology 55, 405-415
Enforced restraint inhibits luteinizing hormone and testosterone secretion.

Puri CP, Puri V, Anand-Kumar TC 1981. Serum levels of testosterone, cortisol, prolactin and bioactive luteinizing hormone in adult male rhesus monkeys following cage-restraint or anaesthetizing with ketamine hydrochloride. Acta Endocrinologica 97, 118-124
Single-housed, adult male rhesus macaques were restrained in their home cages for blood collection at 20 minute intervals. While testosterone levels significantly declined, serum cortisol concentrations significantly increased over a one-hour sampling period.

Quadri SK, Pierson C, Spies HP 1978. Effects of centrally acting drugs on serum levels in rhesus monkeys. Neuroendocrinology 27, 136-147
Immobilization on restraint cross induced progressive increase in prolactin concentration throughout a 60 minute period.

Rabot S, Fisco M, Martin F, Blanquie JP, Popot F, Bensaada M, Vaissade P, Searby N, Szylit O 1997. Effects of chair-restraint on gastrointestinal transit time and colonic fermentation in male rhesus monkey (Macaca mulatta). Journal of Medical Primatology 26, 190-195

"Chair-restraint induced a 2.5-fold acceleration of the gastrointestinal transit time, which persisted throughout the 7 day postrestraint period, and an increase of the fecal dry matter content. "

Reinhardt V, Liss C, Stevens C 1995. Restraint methods of laboratory nonhuman primates: A critical review. Animal Welfare 4, 221-238
"Published information provides scientific evidence that traditional, involuntary restraint techniques of research non-human primates are intrinsically a source of distress resulting from fear."

Schnell CR, Wood JM 1993. Measurement of blood pressure, heart rate, body temperature, ECG and activity by telemetry in conscious unrestrained marmosets. Proceedings of the Fifth Federation of European Laboratory Animal Science Association (FELASA) Symposium, 107-111
Restraining well habituated marmosets by hand significantly increased heart rate and blood pressure even after the animals were returned to their home cages.

Todd HE, Shideler SE, Laughlin LS, Overstreet JW, Pohl CR, Byrd W, Lasley BL 1999. Application of an enzyme immunoassay for urinary follicle-stimulating hormone to describe the effects of an acute stressor at different stages of the menstrual cylce in female laboratory macaques. American Journal of Primatology 48, 135-151
"In the stress study [capture and restraint], we found that stressors occurring during the luteal-follicular transition not only resulted in acute perturbations of FSH but also led to abnormalities in the subsequent menstrual cycle in 50% of the cases."

Torii R, Kitagawa N, Nigi H, Ohsawa N 1993. Effects of repeated restraint stress at 30-minute intervals during 24-hours on serum testosterone, LH and glucocorticoids levels in male Japanese monkeys (Macaca fuscata). Experimental Animal 42, 67-73
"30-min intervals sampling [using "compulsory restraint"] serum testosterone levels decreased and glucocorticoid levels increased, respectively, immediately after the start of blood sampling."

Verlangieri AJ, De Priest JC, Kapeghian JC 1985. Normal serum biochemical, hematological, and EKG parameters in anesthetized adult male Macaca fascicularis and Macaca arctoides. Laboratory Animal Science 35, 63-66
Author underscores undesirable variations in serum biochemical and hematological parameters in macaques and suggests that incongruities between values presented in different reports may be due to a variety of factors including the method of restraint during handling procedures.

Wheeler MD, Schutzengel RE, Barry S, Styne DM 1990. Changes in basal and stimulated growth hormone secretion in the aging rhesus monkeys: A comparison of chair restraint and tether and vest sampling. Journal of Clinical Endocrinology and Metabolism 71, 1501-1507
Animal who "were adapted to chair restraint" appeared calm, but they showed consistently higher cortisol levels than "free moving" tethered animals.

Yasuda M, Wolff J, Howard CF 1988. Effects of physical and chemical restraint on intravenous glucose tolerance test in crested black macaques (Macaca nigra). American Journal of Primatology 15, 171-180
Restrained monkeys "appeared relaxed, but glucose clearance and insulin secretion were impaired" and cortisol values increased.

(8) Queue Effect, Sequential Treatment
Fox MW 1986. Laboratory Animal Husbandry: Ethology, Welfare and Experimental Variables. State University of New York Press, Albany, NY
“The 'queue' effect of treating animals sequentially is an often overlooked experimental variable."

Flow BL, Jaques JT 1997. Effect of room arrangement and blood sample collection sequence on serum thyroid hormone and cortisol concentrations in cynomolgus macaques (Macaca fascicularis). Contemporary Topics in Laboratory Animal Science 36(1), 65-68
Sequence of blood collection [as determined by room arrangement] affected serum cortisol and thyroxine levels.

(9) Unfamiliar Environment

Crockett CM, Bowers CL, Shimoji M, Leu M, Bellanca RU, Bowden DM 1993. Appetite and urinary cortisol responses to different cage sizes in female pigtailed macaques. American Journal of Primatology 31, 305
"Appetite during the first three days in the new room was moderately suppressed."

Crockett CM, Bowers CL, Shimoji M, Leu M, Bowden DM, Sackett GP 1995. Behavioral responses of longtailed macaques to different cage sizes and common laboratory experiences. Journal of Comparative Psychology 109, 368-383
Monkeys who were moved to a new room and to a lesser extent to a new, clean cage showed "disrupted sleep the 1st night and suppressed activity, especially self-grooming, the next day."

*Davenport MD, Lutz CK, Tiefenbacher S, Novak MA, Meyer JS 2007 . A rhesus monkey model of self-injury: Effects of relocation stress on behavior and neuroendocrine function. Biological Psychiatry in press
"Twenty adult male rhesus macaques were exposed to the stress of relocation to a new housing arrangement in a newly constructed facility. .. Our results indicate that relocation is a significant stressor for rhesus macaques and that this stressor triggers an increase in self-biting behavior as well as sleep disturbance in monkeys previously identified as suffering from SIB."

Herndon JG, Turner JJ, Perachio AA, Blank MS, Collins DC 1984. Endocrine changes induced by venipuncture in rhesus monkeys. Physiology & Behavior 32, 673-676
Blood collection in a transport box resulted in elevated GH and cortisol values. "The present data suggest that such responses may complicate interpretation of GH and cortisol measurements derived from samples collected by venipuncture."

Lindburg DG, Coe J 1995. Ark design update: Primate needs and requirements. In Conservation of Endangered Species in Captivity Gibbons EF, Durrant BS, Demarest AJ (eds), 553-570. SUNY Press, Albany
"Wherever possible, every effort should be made to design in ways that bring the treatment to the animal, instead of the reverse. Removal for any purpose exposes the animal to overly novel, frequently noxious, and always stressful, stimuli."

Line SW, Clarke AS, Markowitz H 1987. Plasma cortisol of female rhesus monkeys in response to acute restraint. Laboratory Primate Newsletter 26(4), 1-3
"Confinement in a transfer box was a significant event, as measured by cortisol response, even though this condition was presumably intrinsically less stressful than manual restraint [with the help of the squeeze-back in the home cage]. ... Novelty alone can be a significant source of stress for laboratory primates."

Line SW, Markowitz H, Morgan KN, Strong S 1991. Effect of cage size and environmental enrichment on behavioral and physiological responses of rhesus macaques to the stress of daily events. In Through the Looking Glass. Issues of Psychological Well-being in Captive Nonhuman Primates Novak MA, Petto AJ (eds), 160-179. American Psychological Association, Washington
Adult, single-housed female rhesus macaques responded with a significant rise in heart rate to being removed from their home cage and replaced after the cage had been cleaned. "Once the cage change was completed and the technicians left the room, it was several hours before heart rates returned to the expected level."

Line SW, Morgan KN, Markowitz H, Strong S 1989. Heart rate and activity of rhesus monkeys in response to routine events. Laboratory Primate Newsletter 28(2), 9-12
Adult female rhesus macaques responded with a significant, protracted increase in heart rate to being placed in transfer boxes while their dirty cages were replaced with clean ones. "The mean heart rate remained elevated for two hours after completion of the procedure.... These observations are important to note if one is to avoid confounding the physiological and behavioral effects of experimental manipulations with those induced by routine husbandry."

Mason JW 1972. Corticosteroid response to chair restraint in the monkey. American Journal of Physiology 222, 1291-1294
Animals who were restrained in an unfamiliar environment showed significantly higher urinary cortisol levels than animals who were familiar with the environment in which they were restrained.

Mason JW, Mougey EH, Kenion CC 1973. Urinary epinephrine and norepinephrine responses to chair restraint in the monkey. Physiology and Behaviour 10, 801-803
Animals who were restrained in an unfamiliar environment showed significantly higher unrinary catecholamine levels than animals who were familiar with the environment in which they were restrained.

Mitchell G, Gomber J 1976. Moving laboratory rhesus monkeys (Macaca mulatta) to unfamiliar home cages. Primates 17, 543-547
"The results of this study should serve as a warning to those who wish to observe behavior or take physiological measurements on monkeys. Removing an animal from its home cage prior to monitoring anything biological will probably affect the event being monitored. Behavioral and almost certainly physiological distress occur following removal from the home cage."

Phoenix CH, Chambers KC 1984. Sexual behavior and serum hormone levels in aging rhesus males: Effects of environmental change. Hormones and Behavior 18, 206-215
"Cortisol levels [of single-housed subjects] were significantly higher immediately [one hour] after the move [into another comparable cage in a nearby building] than they were on the first day of bleeding before the move."

Reinhardt V, Cowley D, Eisele S, Scheffler J 1991. Avoiding undue cortisol responses to venipuncture in adult male rhesus macaques. Animal Technology 42, 83-86
Six adult rhesus males were: a) habituated to actively cooperate during venipuncture away from the homecage in a treatment squeeze cage, and b) trained to actively cooperate during venipuncture in the homecage. The magnitude of cortisol increase was significant when the males were venipunctured in the hallways but not when they were venipunctured in the homecage. "It was concluded that venipuncture per se was not a physiologically distressing event. It became distressing only when it was associated with a temporary removal from the homecage."

Schapiro SJ, Nehete PN, Perlman JE, Sastry KJ 1997. A change in housing condition leads to relatively long-term changes in cell-mediated immune responses in adult rhesus macaques. American Journal of Primatology 42, 146
"A change in housing condition results in changes in immune responses, even after subjects had spent up to eight months in the new housing and regardless of whether the change was to solitary or pair housing."

(10) Double-tier Cage Arrangement

*Baumans V, Coke C, Green J, Moreau E, Morton D, Patterson-Kane E, Reinhardt A, Reinhardt V, Van Loo P 2007 Making Lives Easier for Animals in Research Labs - Chapter 9.5. Multi-Tier Caging. Washington, DC: Animal Welfare Institute
"In a quantitative study I did on 20 pair-housed cynos, the animals spent 94 percent of their waking time in the upper part of the vertically arranged double cage. All food was given in the bottom section, yet the animals would bring the food to the upper part and consume it there. The monkeys preference along the gradient of height was unequivocal!
I observed squirrel monkeys in vertically arranged double cages and also found that the animals clearly preferred the upper half of their cages. The only time they went to the bottom half was when they retrieved a toy or picked through the bedding for treats.
When visiting facilities that have their pair-housed macaques kept in vertically arranged double-cages, I repeatedly got the impression that subordinate partners are disadvantaged in this caging system, with dominant animals preventing subordinates from spending as much time in the upper section as they would like to."

Baskerville M 1999. Old World Monkeys. In The UFAW [Universities Federation for Animal Welfare] Handbook on the Care and Management of Laboratory Animals Seventh Edition Poole T, English P (eds), 611-635. Blackwell Science, Oxford
"Captive primates like to move upwards and look down on unfamiliar humans, and ideally the cage height should allow this. Two tier caging should be avoided."

Box HO, Rohrhuber B 1993. Differences in behaviour among adult male, female pairs of cotton-top tamarins (Saguinus oedipus) in different conditions of housing. Animal Technology 44, 19-30
Animals living in upper-row cages were more active and engaged in more close contact amicable behavior than animals living in lower-row cages.

Clough G 1982. Environmental effects on animals used in biomedical research. Biological Reviews 57, 487-523
"The intensity of light in animal cages is likely to be the most variable environmental factor in the average animal room."

European Commission 2002. The Welfare of Non-human Primates - Report of the Scientific Committe on Animal Health and Animal Welfare. European Commission, Strasbourg, Francehttp://europa.eu.int/comm/food/fs/sc/scah/out83_en.pdf
"Primates should not be placed in double-tiered caging unless the arrangement permits adequate vertical movement for the animal."

Heger W, Merker H-J, Neubert D 1986. Low light intensity decreases the fertility of Callithrix jacchus. Primate Report 14, 260
"Improvement of the light fixtures in both rooms doubled the lighting force and increased the breeding rate during the following 12 months approximately 20% in the upper and 130% in the lower cages."

Mahoney CJ 1992. Some thoughts on psychological enrichment. Lab Animal 21(5), 27,29,32-37
"The sanitation tray, which runs the length of the room beneath the upper tier of cages, reduces significantly the amount of light from ceiling-mounted fixtures that can penetrate to the lower cage tier; animals in the lower tier are thus relegated to a permanent state of semi-gloom."

Mulder JB 1976. Behavior patterns of laboratory animals. Lab Animal 5(5), 22-28
"Placing of the cage on a rack even further reduces the available light. During experimentation, care must be exercised to use cages of the ... same placement to avoid variations in lighting. If this is not done, the investigator may be measuring behavioral rather than experimental results."

National Research Council 1998. The Psychological Well-Being of Nonhuman Primates. National Academy Press, Washington
"Wild marmosets and tamarins only occasionally descent to the ground and in captivity prefer to be above caregiving personnel. Therefore, it is advisable not to house these primates in two-tier cages. ... Under natural conditions, many primates spend much of their lives aboveground and escape upward to avoid terrestrial threats. Therefore, these animals might perceive the presence of humans above them as particularly threatening. ... Even macaques, which some describe as semiterrestrial, spend most of the day in elevated locations and seek the refuge of trees at night."

Reinhardt V 1989. Evaluation of the long-term effectiveness of two environmental enrichment objects for singly caged rhesus macaques. Lab Animal 18(6), 31-33
"The proportion of time spent with the pipes was three times greater for animals living in lower-row cages than for animals living in upper-row cages. ... In the elevated position, the light exposure was increased, a fact that made the pipes of particular value for the lower-row cages animals."

Reinhardt V, Reinhardt A 2000. The lower 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 that cage location of research monkeys is usually not mentioned (98%), in spite of the fact that the environment of upper- and lower-row housed animals markedly differs in terms of light quality, light intensity and living dimension. Not accounting for these uncontrolled variables may increase variability of data and, consequently, the number of experimental animals needed to obtain statistically acceptable results."

Reinhardt V, Reinhardt A 1999. The monkey cave: The dark lower-row cage. Laboratory Primate Newsletter 38(3), 8-9
"The typical lower-row cage provides a cave-like housing environment which may impair well-being, invalidate research data, and undermine good housekeeping."

Ross PW, Everitt JI 1988. A nylon ball device for primate environmental enrichment. Laboratory Animal Science 38(4), 481-483
"We feel that macaques fare better when they are housed in cages on the upper tier or racks. This may relate to better interactions with the animal care technicians when they are housed in this position."

Schapiro SJ, Bloomsmith M 2001. Lower-row caging in a two-tiered housing system does not affect the behaviour of young, singly housed rhesus macaques. Animal Welfare 10, 387-394
"Although lower-row cages are significantly darker than upper-row cages at our facility, the data from the present study demonstrate that the diminished lighting and other supposed disadvantages experienced by lower-row-housed monkeys have few behavioural consequences" [under undisturbed conditions].

Seier JV, Loza J, Benjamin L 2004. Housing and stereotyped behaviour: Some observations from an indoor colony of vervet monkeys (Chlorocebus aethiops). Folia Primatologica 75(Supplement 1), 332
”Both sexes housed in the upper rows spent less time engaging in stereotyped behaviour.”

Schapiro SJ, Stavisky R, Hook M 2000. The lower-row cage may be dark, but behaviour does not appear to be affected. Laboratory Primate Newsletter 39(1), 4-6
The situation of 3 upper-row single-caged females was compared with that of 6 lower-row single-caged females under undisturbed conditions. Mean light levels at nine different positions within the cage were significantly lower in bottom-row cages than in upper-row cages. "Less than 8% of light readings in lower-row cages were higher than the lowest light level readings at the same position in the upper-row cages. .... There were no statistically significant differences in behavior [abnormal, inactivity, grooming, drinking, feeding, exploring, lip smacking]." The mean percent time spent in abnormal behavior was 0.7 for upper-row caged subjects versus 1.6 for lower-row caged subjects.

Shimoji M, Bowers CL, Crockett CM 1993. Initial response to introduction of a PVC perch by singly caged Macaca fascicularis. Laboratory Primate Newsletter 32(4), 8-11
Single-housed "monkeys spent significantly more time clinging to the cage wall ("suspended") in the absence of the perch. ... Monkeys in lower level cages averaged somewhat more time on the perch than those in upper cages."

Shively CA 2001. Psychological Well-Being of Laboratory Primates at Oregon Regional Primate Research Center. Web site link in Willamette Week (Portland), March 21, 2001
"We have observed lower body weights in animals housed in lower tier cages."

Woodbeck T, Reinhardt V 1991. Perch use by Macaca mulatta in relation to cage location. Laboratory Primate Newsletter 30(4), 11-12
Single-housed "animals living in lower-row cages spent an average of 31.6% of the time perching on their pipes while animals living in upper-row cages perched only 6.9% of the time. Access to the vertical dimension of the cage was more important for the lower-row caged monkeys who continuously live close to the ground, in the horizontal dimension of the room."

(11) Neighbor Effect

Aureli F, Seres M, Whitten PL, de Waal FB 2001. Living conditions affect stress levels of captive chimpanzees. American Journal of Primatology 54(Supplement 1), 67-68
"Our results indicate that stress levels in captive chimpanzees are not affected by population density per se (chimpanzees use behavioural coping strategies), but when coupled with high Neighbor Effect stress levels increase. If many groups need to live in close proximity, it is better to house chimpanzees in large compounds."

Baker KC, Aureli F 1996. The neighbor effect: Other groups influence intragroup agonistic behavior in captive chimpanzees. American Journal of Primatology 40, 283-291
Hearing the vocalizations of neighboring groups increased the likelihood of intragroup fighting. "It may be indicated to construct corrals at a distance from each other to avoid this undesirable neighbor effect."

Coe CL 1991. Is social housing of primates always the optimal choice? In Through the Looking Glass. Issues of Psychological Well-being in Captive Nonhuman Primates. Novak MA, Petto AJ (eds), 78-92. American Psychological Association, Washington
"In a recent longitudinal assessment of six pairs of male rhesus monkeys, ... we found that introduction of female subjects into the housing area had a significant effect on other physiological systems, including the immune systems, of these male pairs. For example, both dominant and subordinate males showed a month-long decline in the natural killer-cell activity following the psychological stimulation evoked by housing two females in cages adjacent to the cages of the male pairs."

Kurth B, Bryant D 1998. Pairing female Macaca fascicularis. Laboratory Primate Newsletter 37(4), 3
Twenty-nine previously single-caged adult female long-tailed macaques were paired with each other in vertical, double-cage configuration. "Neighboring pairs were often charging each other across the grid panel. ... To avoid this, pairs were transferred to a horizontal configuration after the first month."

Lipman NS 1992. Large colonies vs. small colonies. In Implementation Strategies for Research Animal Well-Being: Institutional Compliance with Regulations Krulisch L (ed), 145-150. Scientist Center for Animal Welfare and WARDS, Bethesda
"It is important to recognize that visual contact between incompatible conspecifics can lead to problems such as anorexia and stereotypic behavior. Therefore our caregivers and veterinary staff pay close attention to the cage arrangement [of the single-caged animals] within each room."

Wallis J, King BJ 1986. The effect of female proximity and social interaction on the menstrual cycle of crab-eating monkeys (Macaca fascicularis). Primates 27(1), 83-94
"Close physical contact and social interaction between female crab-eating monkeys affects the reproductive cycle: females with a history of irregular and/or unusually long cycles began exhibiting more normal cycling patterns when placed in proximity to a regularly cycling female. Irregular controls continued to show cycles that were abnormally long."

(12) Observer Effect, Presence of Personnel

Boinski S, Gross TS, Davis JK 1999. Terrestrial predator alarm vocalizations are a valid monitor of stress in captive brown capuchins (Cebus apella). Zoo Biology 18, 295-312
"We have most commonly, but certainly not always, documented TPAs [terrestrial predator alarms] being produced in association with the entrance into or presence of humans in colony rooms. Most predictably those humans are research technicians associated with manipulative research projects involving the capuchins. ... Mean TPA production was correlated to fecal cortisol and behavioral disorders. "

Bowers CL, Crockett CM, Bowden DM 1998. Differences in stress reactivity of laboratory macaques measured by heart period and respiratory sinus arrhythmia. American Journal of Primatology 45, 245-261
"Exposure to an unfamiliar technician with capture gloves stimulated cardiac reactivity more strongly than an intense sound. ... Behavior responses to the glove indicated that all subjects consistently perceived this 'ecologically relevant' stimulus as threatening."

Line SW, Morgan KN, Markowitz H, Strong S 1989. Heart rate and activity of rhesus monkeys in response to routine events. Laboratory Primate Newsletter 28(2), 9-12
"Variations in heart rate and activity are closely associated with human activity in the room."

Line SW 1995. Effects of observation technique on the behavior of adult rhesus macaques. Contemporary Topics in Laboratory Animal Science 34, 61-65
"During videotaped sessions, movement was higher in frequency and duration, while aggressive behavior was lower" and stereotyped locomotion higher in frequency than during direct live observations.

Malinow MR, Hill JD, Ochsner AJ 1974. Heart rate in caged rhesus monkeys (Macaca mulatta). Laboratory Animal Science 24, 537-540
Heart rate of single-housed subjects increased coincident with human activity in the animal room, reaching peaks during feeding and cleaning. "The rapid increase of 80 beats/min recorded when someone entered the room and tapped the cages is most probably related to the action of the autonomic nervous system and may explain the high heart rates reported in most studies of restrained or anesthetized monkeys. Thus, when the results of cardiovascular studies in rhesus monkeys are interpreted, the variables introduced by the sympathetic or parasympathetic nerves should be considered."

Manuck SB, Kaplan JR, Clarkson TB 1983. Behavioral induced heart rate reactivity and atherosclerosis in cynomolgus monkeys. Psychosomatic Medicine 45, 95-108
The presence of the experimenter [without glove!] dramatically increased heart rate in about 50% of animals studied.

Reinhardt V 1999. Pair-housing overcomes self-biting behavior in macaques. Laboratory Primate Newsletter 38(1), 4
Seven single-caged subjects exhibited self-biting behavior predictably in the presence of personnel.

Reinhardt V 1997. Refining the traditional housing and handling of laboratory rhesus macaques improves scientific methodology. Primate Report 49, 93-112
"It cannot be overemphasized how critical the role of personnel is in determining the animals' well-being, and hence their 'quality' as research subjects. The macho-type person is out of place in the animal room because s/he triggers stress or even distress reactions. Typically, the animal will freak out and hide in a back corner of the cage when such a person comes into their room."

Schnell CR, Wood JM 1993. Measurement of blood pressure, heart rate, body temperature, ECG and activity by telemetry in conscious unrestrained marmosets. Proceedings of the Fifth Federation of European Laboratory Animal Science Association (FELASA) Symposium, 107-111
"After event A [presence of a person], we observed a twofold increase in activity and a marked increase in CT [temperature], MAP [blood pressure] and HR [heart rate]."

Schnell CR, Wood JM 1993. Measurement of blood pressure and heart rate by telemetry in conscious, unrestrained marmosets. American Journal of Physiology 264(Heart Circulatory Physiology 33), H1509-1516
During the weekend, daytime values of heart rate and blood pressure were significantly lower, and motor activity was higher. "The higher motor activity suggests greater social interactions when the marmosets are undisturbed. The lower MAP [blood pressure] and HR [heart rate] suggest that the animals may be less anxious and feel better in this situation."

Tatoyan SK, Cherkovich GM 1972. The heart rate in monkeys (Baboons and Macaques) in different physiological states recorded by radiotelemetry. Folia Primatologica 17, 255-266
"In the presence of man the heart rate is always increased, in spite of the fact that the monkeys appear to be calm."

Tinklepaugh OL 1928. The self-mutilation of a male Macacus rhesus monkey. Journal of Mammalogy 9, 293-300
A drastic case of observer-induced self-biting of a male rhesus macaques is described.

(13) Noise

Baldwin AL, Schwartz GE, Hopp DH 2007. Are investigators aware of environmental noise in animal facilities and that this noise may affect experimental data? Journal of the American Association for Laboratory Animal Science [Contemporary Topics in Laboratory Animal Science] 46(1)
"Because faculty are the least aware of noise as a potential problem but are primarily responsible for designing experiments, research involving animals may be confounded by noise as an unknown variable. This effect may lead to unnecessary numbers of animals being required to achieve statistical significance and possibly to erroneous interpretation of results. On the basis of the findings of this survey, we present recommendations for improving the environment, particularly for decreasing the noise level, in animal facilities."

Patterson-Kane EG, Farnworth MJ 2006. Noise exposure, music, and animals in the laboratory: A commentary based on Laboratory Animal Refinement and Enrichment Forum (LAREF) discussions. Journal of Applied Animal Welfare Science 9, 327-332
"Evidence supports the use of quiet music during nonhuman animals' activity periods, if this practice is introduced with an awareness of the risks to welfare and research."

Pines MK, Kaplan G, Rogers LJ 2004. Stressors of common marmosets (Callithrix jacchus) in the captive environment: Effects on behaviour and cortisol levels. Folia Primatologica 75(Supplement 1), 317-318
Salivary cortisol samples, collected using a cotton bud with banana on the tip, doubled following 30 minutes of exposure to playing radio (70-80 dB) or loud construction work (70-80 dB). Despite being sheltered from rain while outdoors, the marmosets moved indoors voluntarily when it was raining. ”There was no change in cortisol levels following the non-traumatic death of a cage/room mate, however, cortisol levels doubled (and remained elevated for at least five days) following the accidental injury and death of a cage/room mate in the absence of any other disturbing event. Involvement of room-mates in non-invasive experiments was also stressful, with cortisol levels doubling. Activity levels and time spent on the floor of the cage decreases, but there was no change in other stress-indicative behaviours. It would seem that the marmosets might be using a passive coping technique to deal with stressors over which they have no control. The results suggest that marmosets are negatively affected by noise and any kind of event adversely affecting a room-mate.“

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