Blood Collection Procedure of Laboratory Primates: A Neglected Variable in Biomedical Research

Viktor Reinhardt and Annie Reinhardt

Animal Welfare Institute 
Washington, DC


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 cased 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.

Blood collection is a procedure to which laboratory primates are commonly subjected, as most biomedical research parameters are extracted from blood specimens. Usually, forceful manual or mechanical restraint is applied (e.g., Moreland, 1965, Fig. 7; Fielder, & Casmer, 1966, Fig. 3; Schultea, & Stein, 1981, Fig. 1; Reinhardt, 1998, Fig. 2a) or ketamine [a sedative/anesthetic] injected to immobilize the subject (International Association of Microbiological Societies, 1969; Fowler, 1995), because it is traditionally believed that the animals are difficult and even dangerous to handle (e.g., Gisler, Benson, & Young, 1960; Ackerley, & Stones, 1969; Valerio, Miller, Innes, Courtney, Pallotta, & Guttmacher, 1969; Altman, 1970; Whitney, Johnson, & Cole, 1973; Henrickson, 1976; Robbinson, Zwick, Leedy, & Stearns, 1986), and that it would take too long to train subjects to voluntarily cooperate – rather than resist – during the procedure (e.g., Klein & Murray, 1995; Hrapkiewicz, Medina, & Holmes, 1998). Needless to say, forceful restraint is usually also employed for ketamine injection (e.g., Ackerley, & Stones, 1969, Fig. 3). In either way, there is a high probability that being restrained and subjected to a potentially painful handling procedure is a distressing experience not only for a human but also for a nonhuman primate (cf. Public Health Service, 1996), particularly when the operation takes place in a treatment room rather than in the familiar home environment (cf. National Research Council, 1998). The stress reactions affect normal physiological functions making it impossible to interpret research data accurately. It's very simple: "Stressed animals do not make good research subjects" (American Medical Association, 1992, p. 18). Many biomedical investigators using primates as research models have specified this methodological concern.

Bush, Custer, Smeller, and Bush (1977) cautioned that the stress placed on a primate during blood collection involving restraint must be recognized as a data-influencing variable if the experimental procedure is to be considered scientifically reliable. Morton, Abbot, Barclay, Close, Ewbank, Gask, Heath, Mattic, Poole, Seamer, Southee, Thompson, Trussell, West, and Jennings (1993) recommended that it is in the interest of good science, as well as of animal welfare, to check the method of blood sampling for any physiological changes associated with restraint stress. Ferin, Carmel, Warren, Himsworth, and Frantz (1976) and Wickings and Nieschlag (1980) observed that primates are readily alarmed by restraint, and that it may be difficult to obtain stable control levels for hormones which are influenced by stress.

Mason, Wool, Wherry, Pennington, Brady, and Beer (1968) and Herndon, Turner, Perachio, Blank, and Collins (1984) demonstrated that growth hormone secretion is extremely sensitive to the psychological disturbance associated with restraint, complicating the interpretation of blood sample measurements. Fuller, Hobson, Reyes, Winter, and Faiman (1984) warned that determination of basal levels of reproductive hormones presents a problem since restraint for venipuncture may introduce sufficient stress to change endocrine secretion. The authors found that ketamine doesnot eliminate the stress which results from restraint during injection of the drug. Elvidge, Challis, Robinson, Roper, and Thorburn (1976) and Line, Markowitz, Morgan, and Strong (1991) made a similar observation, and Crockett, Bowers, Sackett, and Bowden (1993) recommended that this technique of sedation should be used judiciously because of its impact on research data. Aidara, Tahiri-Zagret, and Robyn (1981) noticed that enforced injection of ketamine resulted in a significant increase in serum prolactin, and assumed that the stress related to the injection could have been the cause of this increase. Findings of Castro, Rose, Green, Lehner, Peterson, and Taub (1981) made it clear that ketamine itself is unlikely to affect endocrine parameters.

Loomis, Henrickson, and Anderson (1980) and Wall, Worthman, and Else (1985) underscored that restraining a macaque to facilitate venipuncture or injection represents a stressful situation, which results in hematological alterations and, therefore, must be taken into account when assessing normal values and when interpreting experimental data. Ives and Dack (1956) termed this phenomenon as "alarm reaction" (p. 728). Verlangieri, De Priest, and Kapeghian (1985) found undesirable variations in serum biochemical parameters (cf. Cope & Polis, 1959) and proposed that incongruities between values presented in different reports may partly be due to the method of restraint during blood collection. Streett and Jonas (1982) cautioned that restraint may introduce major variables preventing the establishment of baseline plasma glucose tolerance curves.

Mason (1972) and Mason, Mougey, and Kenion (1973) noted that macaques show significantly higher urinary cortisol and catecholamine levels when they are restrained in a strange versus a familiar environment. The authors inferred that the familiarity of the location in which the restraint procedure occurs is a dependent variable which contributes to the variance of research data. This implies that the stress response to being removed from the home cage affects subsequently collected scientific data even before the animal is exposed to the additional stress associated with venipuncture and the actual experiment. Reinhardt, Cowley, Eisele, and Scheffler (1991) took blood from macaques on different days in their home cage and in a treatment cage located in the hallway. Cortisol response to venipuncture was significantly higher in the hallway than in the home cage, suggesting that removing an individual from the usual environment may already skew the interpretation of experimental findings independently of the stress that may accrue from venipuncture. This inference is supported by the fact that the animals exhibit behavioral signs of distress (Mitchell & Gomber, 1976) – including supression of activity, sleep and appetite (Crockett, Bowers, Sackett, & Bowden, 1993) – and elevated costisol levels when being removed from their home cages (Line, Clarke, & Markowitz, 1987) and transferred to identical cages in a different room (Phoenix & Chambers, 1984; Crockett, Bowers, Shimoji, Leu, Bowden, & Sackett, 1995).

As a result of adverse conditioning (Nahon, 1968; Robbins, Zwick, Leedy, & Stearns, 1986), primates used for biomedical research typically show signs of apprehension, fear and excitation when an investigator or technician enters their room (Tatoyan & Cherkovich, 1972; Malinow, Hill, & Ochsner, 1974; Manuck, Kaplan, and Clarkson, 1983; Line, Morgan, Markowitz, & Strong, 1989; Schnell, 1997; Boinski, Gross, & Davis, 1999; cf. Reinhardt & Reinhardt, 2000a, Figs. 63 & 64). The magnitude of the alarm reaction and its impact on research findings will depend on the time lapse from entry until the ketamine injection or venipuncture occurs. Often, several animals of a room are handled in succession, and the time lapse will therefore differ for each subject, introducing uncontrolled variability into the reseach data. Disturbance time – or "the `queue' effect of treating animals sequentially" (Fox, 1986, p. 36) – is a critical variable which needs to be taken into consideration for data-quality reason. Flow and Jaques (1997), for example, cautioned that disturbance time can affect thyroid hormone levels in macaques and hence has important implications for research studies that are designed to detect differences in thryoid function among experimental groups. Boccia, Broussard, Scanlan, and Laudenslager (1992), demonstrated that cortisol measures are highly correlated with disturbance time. Capitanio, Mendoza, and McChesney (1996) found that the numbers of CD8+ lymphocytes [a stress-sensitive hematological parameter] were 50% higher in macaques sampled 6-9 minutes after the investigor's initial entry into the room than in subjects sampled after a time lapse of `only' 3-6 minutes. The authors suggested that such variation might lead to inaccurate research results.

There are a few reports which offer solutions to the problem of data-confounding stress effects resulting from the blood collection procedure.

Dettmer, Phillips, Rager, Bernstein, and Fragaszy (1996) carefully habituated capuchin monkeys to the mechanical restraint during venipuncture; subjects exhibited no significant cortisol response as opposed to experienced but non-habituated subjects. Yeoman, Williams, Hazelton, Ricker, and Abee (1988) avoided in squirrel monkeys elevations of estradiol and luteinizing hormone levels resulting from ketamine injection by thoroughly habituating the animals to blood collection involving manual restraint without prior sedation. Findings of Golub and Anderson (1986), Line, Markowitz, Morgan, and Strong (1991) and Schnell and Wood (1993) indicate that rhesus macaques and marmosets are more difficult to habituate to being restrained for injection or venipuncture. Streett and Jonas (1982), however, were able to habituate stump-tailed macaques with a positive reinforcement method so well to being restrained during blood collection that reliable glucose tolerance testing could be performed. Hearn (1982) habituated marmosets to a restraint device for blood sampling and states – without providing supportive data – "that measurements of adrenocortical hormones and prolactin show that the animals are not affected by stress" (p. 139), or at least that the apparatus allows a small monkey to be restrained with a "minimum of stress" (Hearn, 1977, p. 262).

Several authors have reported that they worked with laboratory primates who were trained to voluntarily present a limb for injection: baboons (Levison, Fester, Nieman, & Findley, 1964), mandrills (Priest, 1991), and chimpanzee (Byrd, 1977; Laule, Thurston, Alford, & Bloomsmith, 1996; Reichard, & Shellaberger, 1992).

However, as yet there is no experimental evidence that cooperative animals show less physiological stess reactions than subjects who are restrained during injection. Photographs and videotape scenes of unrestrained rhesus macaques who were trained to cooperate during injection in the home cage demonstrate very clearly that the subjects experienced, at least, no psychological stress (Reinhardt, & Dodsworth, 1989, Scenes 11 & 22; Reinhardt, 1992, Fig. 3; Reinhardt, 1997, Fig. 18; Reinhardt, & Reinhardt, 2000b, Fig. 2).

Elvidge, Challis, Robinson, Roper, and Thorburn (1976) trained macaques to offer a leg for blood sampling, and achieved cortisol values which were significantly lower than those of untrained or ketamine-injected animals. Michael, Setchell, and Plant (1974) evaluated cortisol concentrations in macaques who were trained to enter a restraining apparatus and permit venipuncture without showing behavioral signs of stress. Values were 30% lower than had previously been reported for untrained animals. Reinhardt (1992) observed that the typical, significant cortisol response and acute fear reactions during blood collection on treatment tables or in treatment cages can be avoided if the subject is trained to cooperate in his/her familiar home cage. Vertein and Reinhardt (1989), Reinhardt (1991) and Reinhardt and Cowley (1992) spent less than a cumulative total of 45 minutes per subject to train adult rhesus and stump-tailed macaques to cooperate during in-home cage blood sampling. The time investment quickly paid off in a strict control of the time lapse from initial entry into the room until completion of blood collection: The range of disturbance time was only 1-2 minutes, compared to 1-20 minutes reported for untrained animals (e.g., Capitanio, Mendoza, & McChesney, 1996).

Successful training for cooperation in venipuncture has been reported by numerous investigors not only for macaques (cf. Bernstein, Rose, & Gordon, 1977; Rosenblum & Coulston, 1981; Bunyak, Harvey, Rhine, & Wilson, 1982; Hein, Schatorje, Frencken, & Segers, 1989; Scallet, McKay, Bailey, Ali, Paule, Slikker, & Rayford, 1989; Phillippi-Falkenstein & Clarke, 1992; Eaton, Kelley, Axthelm, Iliff-Sizemore, & Shiigi, 1994) but also for vervet monkeys (Suleman, Njugana, & Anderson, 1988), baboons (Chambers, Gibson, Bindman, Guillou, Herbert, Mayes, Pool, Wade, & Wood, 1992), mandrills (Priest, 1990), chimpanzees (T-W-Fiennes, 1972; McGinnis & Kraemer, 1979; Laule, Thurston, Alford, & Bloomsmith, 1996), and marmosets (Moseley & Davis, 1989). The Home Office (1989), the International Primatological Society (1989) and the National Research Council (1998) underline the importance of training in order to reduce the stress of restraint and to promote quality data (cf. Klein & Murray, 1995; Baskerville, 1999; Laule, 1999). In addition, training nonhuman primates to cooperate rather than resist during blood collection increases the safety of the personnel since the research subject is no longer given any reason for self-defense reactions such as biting or scratching (Anderson, & Houghton, 1983; Reinhardt, 1991; Reichard, & Laule, 1993).

One of the fundamental principles of scientific biomedical methodology is the rigorous control of extraneous variables which might influence the variability of research data and hamper the replication of the study by other laboratories (Claassen, 1994; Woolley, 1997). "Unless these requirements are met, an experiment is not considered scientifically valid" (American Medical Association, 1992, p. 5). This is one reason why laboratory animals – including nonhuman primates – are often kept under standardized, extremely boring housing conditions. The present article tests the hypothesis that biomedical investigators also take variables into account which pertain to the blood collection procedure as an assurance for scientific validity of the research methodology.



A survey was conducted of all scientific articles published since inception in the Journal of Medical Primatology (Vols. 1-28) and the Journal of American Primatology (Vols. 1-49). Studies assessessing stress-sensitive blood parameters were screened for the following methodological details (variables):

1. Was the subject sedated with ketamine prior to venipuncture?

2. How long did it take from entering the animal room to injection of ketamine and venipuncture, respectively?

3. Where did the injection of ketamine, and where did venipuncture take place?

4. How was the subject handled during injection and venipunture, respectively? 



A total of 75 scientific articles were dealing with one or several stress-sensitive parameters (Table 1) in blood collected from caged macaques (58), vervet monkeys (7), capuchin monkeys (4), marmosets (3), squirrel monkeys. (2), and baboons (1). Regarding the first variable, 76 % of the studies specify whether or not the research subjects were injected with ketamine prior to venipuncture (Table 2). Twelve percent of the studies mention the time lapse from the investigator's entry into the animal room to ketamine injection (1%) or venipuncture (11%; Table 2). Sixteen percent of the studies disclose if the research subjects were injected or venipunctured in their home cages or away from them in corridors or treatment areas (Table 2), and 27% of the studies explain if the research subjects were habituated or trained for injection or venipuncture, or if they were forcefully restrained during these procedures (Table 2). Seventy-two percent of the articles provide no information (16) or mention only one (38) of the four variables pertaining to the blood collection procedure. Twenty-eight percent (21/75) of the articles elaborate on two (9), three (10) or all four (2) of these variables.





 Parameters Assessed in Articles Surveyed
Reproductive hormones 
Adrenocorticotrophic hormone 
Growth hormone
Immune stress response
Serum chemistry






 Details of Blood Collection Procedure Disclosed in Articles Surveyed


(1) Is the subject injected with Ketamine prior to venipuncture?
(a) Yes
(b) No
(c) Not mentioned
18 (24%)
(2) What it the time lapse from intry into the room to injection/venipuncture?
(a) 2 minutes (injection)
(b) 1-20 minutes (venipuncture)
(c) Not mentioned
66 (88%)
(3) Where does injection/venipuncture take place?
(a) In home cage
(b) Away form home cage
(c) Not mentioned
63 (84%)
(4) How is the subject handled during injection/venipuncture?
(a) Subject is habituated
(b) Subject is trained to cooperate
(c) Subject is restrained
(d) Not mentioned
55 (73%)



The present survey indicates that many primatological investigators are unaware of (c.f Arluke, 1988) or do not think it is important or critical how their research subjects are handled (cf. Traystman, 1987). They disregard the fact that the blood collection procedure can be a stressful event which could affect scientific results, or at least they do not adequately describe the dependent variables which are tied to it. The conditions under which blood samping occurred were described in most instances so haphazardly or not at all that it would be impossible to determine if stress-related variables have distorted the research findings. This circumstance also makes it difficult, if not impossible, to replicate the experiment regardless of its scientific merit (cf. Claassen, 1994; Öbrink & Rehbinder, 1999). The same situation has been highlighted by Davis, Bennett, Berkson, Lang, Snyder, and Pick (1973) for laboratory rodents. The authors concluded from a survey of 191 scientific articles that "It is most distressing to find that the frequency of handling the animals [for procedures] was mentioned in only a single article [0.5%] of the entire lot" (p. 3).

The primatological literature testifies that some investigators are aware that enforced restraint during injection, enforced restraint during venipucture, unfamiliarity of environment, and disturbance time are variables of the blood collection procedure which are relevant for a meaningful interpretation of stress-sensitive research data. To ignor these variables while ascertaining at the same time that `basal' or `normal' values of stress-sensitive blood paramters were determined, would contravene basic scientific rules. The literature also documents numerous reports of researchers who have made successful attempts to control these variables by working with animals who were trained to cooperate during swift blood collection in their familiar home cages.

To safeguard the integrity of scientific methodology and the humane treatment of primates used in research, the following guidelines should be observed:

1. Investigators should consider how physiological changes resulting from compulsory restraint affect their proposed experiments (Olfert, Cross, & McWilliam, 1993).

2. Editors of scientific journals should require that authors provide sufficient information on the blood collection – and when applicable also of the ketamine injection procedure so that the investigation can be replicated reliably in another laboratory (cf. Davis, Bennett, Berkson, Lang, Snyder, & Pick, 1973; Öbrink & Rehbinder, 1999) and the research data interpreted with reasonable accuracy.

It is not only a scientific but also an ethical obligation to describe variables of the blood collection procedure unless it has been proven beforehand or documented in the scientific literature that these do not stress the research subject and that they do not influence the data collected from it. Uncontrolled variables introduced by ketamine injection or venipuncture automatically increase data variability and hence the number of research subjects needed to achieve statistical significance (cf. Russell, & Burch, 1959; Brockway, Hassler, & Hicks, 1993; Hau & Craver, 1994). This is not necessary if published refinement techniques are applied which allow the research primate to be a cooperative partner rather than a subdued subject during the handling procedure (cf. T-W-Fiennes, 1972; Schnell & Gerber, 1997). Since "scientists themselves have adopted the principle: `Good Animal Care and Good Science Go Hand in Hand'" and since institutions are "obliged to adhere to the highest possible standards for the humane care and responsible use of laboratory animals" (Public Health Service, 1994, p. 12), it must be considered unethical if an investigator through carelessness or ignorance uses more animals for a project and hence inflicts more suffering than is absolutely necessary (cf. Öbrink & Rehbinder, 1999).




Ackerley, E. T., & Stones, P. B. (1969). Safety procedures for handling monkeys. Laboratory Animal Handbooks, 4, 207-211.

Aidara, D., Tahiri-Zagret, C., & Robyn, C. (1981). Serum prolactin concentrations in mangabey (Cercocebus atys lunulatus) and patas (Erythrocebus patas) monkeys in response to stress, ketamine, TRH, sulpiride and levodopa. Journal of Reproduction and Fertility, 62, 165-172.

Altman, N. H. (1970). Restraint of monkeys in clinical examination and treatment. Journal of the American Veterinary Medical Association, 159, 1222.

American Medical Association (1992). Use of Animals in Biomedical Research: The Challenge and Response. An American Medical Association White Paper. Chicago: AMA. Group on Science and Technology.

Anderson, J. H., & Houghton, P. (1983). The pole and collar system. A technique for handling and training nonhuman primates. Lab Animal, 12 (6), 47-49.

Arluke, A. B. (1988). Sacrifical symbolism in animal experimentation: Object or pet? Anthrozoos, 2, 98-117.

Bernstein, I. S., Rose, R. M., & Gordon, T. P. (1977). Behavioural and hormonal responses of male rhesus monkeys introduced to females in the breeding and non-breeding seasons. Animal Behaviour, 25, 609-614.

Boccia, M. L., Broussard, C., Scanlan, J. & Laudenslager, M. L. (1992). Practice makes predictable: The differential effect of repeated sampling on behavioral and physiological responses in monkeys. In H. Davis, & A. D. Balfour (eds), The Inevitable Bond: Examining Scientist-Animal Interactions (pp. 153-170) New York: Cambridge University Press.

Boinski, S., Gross, T. S., & Davis, J. K. (1999). Terrestrial predator alarm vocalizations are a valid monitor of stress in captive brown capuchins (Cebus apella). Zoo Biology, 18, 295-312.

Brockway, B. P., Hassler, C. R., & Hicks, N. (1993). Minimizing stress during physiolgical monitoring. In S. M. Niemi, & J. E. Willson (eds), Refinement and Reduction in Animal Testing (pp. 56-69) Greenbelt, MD: Scientists Center for Animal Welfare.

Bunyak, S. C., Harvey, N. C., /Rhine, R. J., & Wilson, M. I. (1982). Venipuncture and vaginal swabbing in an enclosure occupied by a mixed-sex group of stumptailed macacaques (Macaca arctoides). American Journal of Primatology, 2, 201-204.

Bush, M., Custer, R., Smeller, J, & Bush, L. M. (1977). Physiologic measures of nonhuman primates during physical restraint and chemical immobilization. Journal of the American Veterinary Medicine Association, 171, 866-869.

Byrd, L. D. (1977). Introduction: Chimpanzees as biomedical models. In G. H. Bourne (ed), Progress in Ape Research (pp. 161-165) New York: Academic Press.

Capitanio, J. P., Mendoza, S. P., & McChesney, M. (1996). Influence of blood sampling procedures on basal hypothalamic-pituitary-adrenal hormone levels and leukocyte values in rhesus macaques (Macaca mulatta). Journal of Medical Primatology, 25, 26-33.

Castro, M. I., Rose, J., Green, N., Petersen, D., & Taub, D. (1981). Ketamine-HC1 as a suitable anesthetic for endocrine, metabolic, and cardiovascular studies in Macaca fascicularis. Proceedings of the Society for Experimental Biology and Medicine, 168, 389-394.

Chambers, D. R., Gibson, T. E., Bindman, L., Guillou, P. J., Herbert, W. J., Mayes, P. A., Poole, T. B., Wade, A. J., & Wood, R. K. S. (1992). Guidelines on the Handling and Training of Laboratory Animals. Potters Bar: Universities Federation for Animal Welfare.

Claassen, V. (1994). Neglected Factors in Pharmacology and Neuroscience Research. Amsterdam: Elsevier.

Cope, F. W., & Polis, B. D. (1959). Increased plasma glutamic-oxalacetic transaminase activity in monkeys due to nonspecific stress effect. Journal of Aviation Medicine, 30, 90-94.

Crockett, C. M., Bowers, C. L., Sackett, G. P., & Bowden, D. M.(1993). Urinary cortisol responses of longtailed macaques to five cage sizes, tethering, sedation, and room change. American Journal of Primatology, 30, 55-74.

Crockett, C. M., Bowers, C. L., Shimoji, M., Leu, M., Bowden, D. M., & Sackett, G. P.(1995). Behavioral responses of longtailed macaques to different cage sizes and common laboratory experiences. Journal of Comparative Psychology, 109, 368-383.

Davis, D. E., Bennett, C. L., Berkson, G., Lang, C. M., Snyder, R. L., & Pick, J. R. (1973). ILAR Committe on Laboratory Animal Ethology recommendations for a standardized minimum description of animal treatment. Institute of Laboratory Animal Resources News, 16 (4), 3-4.

Dettmer, E. L., Phillips, K. A., Rager, D. R., Bernstein, I., & Fragaszy, D. M. (1996). Behavioral and cortisol responses to repeated capture and venipuncture in Cebus apella. American Journal of Primatology, 38, 357-362.

Eaton, G. G., Kelley, S. T., Axthelm, M. K., Iliff-Sizemore, S. A., & Shiigi, S. M. (1994). Psychological well-being in paired adult female rhesus (Macaca mulatta ). American Journal of Primatology, 33, 89-99.

Elvidge, H., Challis, J. R. G., Robinson, J. S., Roper, C., & Thorburn, G. D. (1976). Influence of handling and sedation on plasma cortisol in rhesus monkeys (Macaca mulatta). Journal of Endocrinology, 70, 325-326.

Ferin, M., Carmel, P. W., Warren, M. P., Himsworth, R. L., & Frantz, A. G. (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.

Fielder, F. G., & Casmer, C. J. (1966). A device to facilitate the restraint and handling of monkeys with minimal human contact. Laboratory Animal Science, 16, 394-402.

Flow, B. L., & Jaques, J. T. (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.

Fowler, M. E. (1995). Restraint and Handling of Wild and Domestic Animals (Second Edition). Ames: Iowa State University Press.

Fox, M. W. (1986). Laboratory Animal Husbandry. Ethology, Welfare and Experimental Variables. Albany: State University of New York Press.

Fuller. G. B., Hobson, W. C., Reyes, F. I., Winter, J. S. D., & 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.

Gisler, D. B., Benson, R. E., & Young, R. J. (1960). Colony husbandry of research monkeys. Annals of the New York Academy of Science, 85, 758-568.

Golub, M. S., & Anderson, J. H. (1986). Adaptation of pregnant rhesus monkeys to short-term chair restraint. Laboratory Animal Science, 36, 507-511.

Hau, J., & Craver, J. F. A. (1994). Refinement in laboratory animal science. Scandinavian Journal of Laboratory Animal Science, 4, 161-167.

Hearn, J. P. (1977). A device for restraining small monkeys. Laboratory Animals, 11, 261-262.

Hearn, J. P. (1982). The reproductive physiology of the common marmoset Callithrix jacchus in captivity. International Zoo Yearbook, 22, 138-143.

Hein, P. R, Schatorje, J. S., Frencken, H. J., Segers, M. F., & Thomas, C. M. (1989). Serum hormone levels in pregnant cynomolgus monkeys. Journal of Medical Primatology, 18, 133-142.

Henrickson, R. V. (1976). The nonhuman primate. Lab Animal , 5 (4), 60-62.

Herndon, J. G., Turner, J. J., Perachio, A. A., Blank, M. S., & Collins, D. C. (1984). Endocrine changes induced by venipuncture in rhesus monkeys. Physiology & Behavior, 32, 673-676.

Home Office (1989). Animals (Scientific Procedures) Act 1986. Code of Practice for the Housing and Care of Animals Used in Scientific Procedures. London: Her Majesty's Stationery Office.

Hrapkiewicz, K., Medina, L., & Holmes, D. D. (1998). Clincial Medicine of Small Mammals and Primates, Second Edition. London: Manson Publishing.

International Association of Microbiological Societies. (1969). Proposed procedure for the housing and handling of simians to decrease the transmission of disease to man. Laboratory Animal Handbooks, 4, 255-266.

International Primatological Society. (1989). IPS International Guidelines for the acquisition, care and breeding of nonhuman primates. Primate Report, 25, 3-27.

Ives, M., & Dack, G. M. (1956). "Alarm reaction" and normal blood picture in Macaca mulatta. Journal of Laboratory Clinical Medicine, 47, 723-729.

Klein, H. J. , & Murray, K. A. (1995). Part C. Restraint. In B. T. Bennett, C. R. Abee, & R. Henrickson (eds), Nonhuman Primates in Biomedical Research – Biology and Management (pp. 286-297) New York: Academic Press.

Laule, G. (1999). Training laboratory animals. In T. Poole, & P. English (eds), The UFAW Handbook on the Care and Management of Laboratory Animals Seventh Edition (pp. 21-27) Oxford: Blackwell Science.

Laule, G. E., Thurston, R. H., Alford, P. L., & Bloomsmith, M. A. (1996). Training to reliably obtain blood and urine samples from a diabetic chimpanzee (Pan troglodytes). Zoo Biology, 15, 587-591.

Levison, P. K., Fester, C. B., Nieman, W. H., & Findley, J. D. (1964). A method for training unrestrained primates to receive drug injection. Journal of the Experimental Analysis of Behavior, 7, 253-254.

Line, S. W., Clarke, A. S., & Markowitz, H. (1987). Plasma cortisol of female rhesus monkeys in response to acute restraint. Laboratory Primate Newsletter, 26 (4), 1-3.

Line, S. W., Markowitz, H., Morgan, K. N., & 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 M. A. Novak, & A. J. Petto (eds), Through the Looking Glass. Issues of Psychological Well-being in Captive Nonhuman Primates (pp. 160-179) Washington DC: American Psychological Association.

Line, S. W., Morgan, K. N., Markowitz, H., & Strong, S. (1989). Heart rate and activity of rhesus monkeys in response to routine events. Laboratory Primate Newsletter, 28 (2), 9-12.

Loomis, M. R., Henrickson, R. V., & Anderson, J. H. (1980). Effects of ketamine hydrochloride on the hemogram of rhesus monkeys (Macaca mulatta). Laboratory Animal Science, 30, 851-853.

Malinow, M. R., Hill, J. D., & Ochsner, A. J. (1974). Heart rate in caged rhesus monkeys (Macaca mulatta). Laboratory Animal Science, 24, 537-540.

Manuck, S. B., Kaplan, J. R., & Clarkson, T. B. (1983). Behavioral induced heart rate reactivity and atherosclerosis in cynomolgus monkeys. Psychosomatic Medicine, 45, 95-108.

Mason, J. W. (1972). Corticosteroid response to chair restraint in the monkey. American Journal of Physiology, 222, 1291-1294.

Mason, J. W., Mougey, E. H., & Kenion, C. C. (1973). Urinary epinephrine and norepinephrine responses to chair restraint in the monkey. Physiology and Behaviour, 10, 801-803.

Mason, J. W., Wool, M. S., Wherry, F. E., Pennington, L. L., Brady, J.V., & Beer, B. (1968). Plasma growth hormone response to avoidance in the monkey. Psychosomatic Medicine, 30, 760-773.

McGinnis, P. R., & Kraemer, H. C. (1979). The Stanford outdoor primate facility.Comfortable Quarters for Laboratory Animals, Seventh Edition (pp. 20-27) Washington, DC: Animal Welfare Institute.

Michael, R. P., Setchell, K. D. R., & Plant, T. M. (1974). Diurnal changes in plasma testosterone and studies on plasma corticosteroids in non-anaesthetized male rhesus monkeys (Macaca mulatta). Journal of Endocrinology, 63, 325-335.

Mitchell, G., & Gomber, J. (1976). Moving laboratory rhesus monkeys (Macaca mulatta) to unfamiliar home cages. Primates, 17, 543-547.

Moreland, A. F. (1965). Collection and withdrawal of body fluids and infusion techniques. In W. I. Gay (ed), Methods of Animal Experimentation, Volume I (pp. 1-42) New York: Academic Press.

Morton, D. B., Abbot, D., Barclay, R., Close, B. S., Ewbank, R., Gask, D., Heath, M., Mattic, S., Poole, T., Seamer, J., Southee, J., Thompson, A., Trussell, B., West, C., & Jennings, M. (1993). Removal of blood from laboratory mammals and birds. Laboratory Animals, 27, 1-22.

Moseley, J. R., & Davis, J. A. (1989). Psychological enrichment techniques and New World monkey restraint device reduce colony management time. Lab Animal, 18 (7), 31-33.

Nahon, N. S. (1968). A device and techniques for the atraumatic handling of the sub-human primate. Laboratory Animal Care, 18, 486-487.

National Research Council (1998). The Psychological Well-Being of Nonhuman Primates. Washington: National Academy Press.

Öbrink, K. J., & Rehbinder, C. (1999). Animal defintion: a necessity for the validity of animal experiments? Laboratory Animals, 22, 121-130.

Olfert, E. D., Cross, B. M., & McWilliam, A. A. (eds) (1993). Guide to the Care and Use of Experimental Animals, Volume 1, 2nd Edition. Ottawa: Canadian Council on Animal Care.

Phillippi-Falkenstein, K., & Clarke, M. R. (1992). Procedure for training corral-living rhesus monkeys for fecal and blood-sample collection. Laboratory Animal Science, 42, 83-85.

Phoenix, C. H., & Chambers, K. C. (1984). Sexual behavior and serum hormone levels in aging rhesus males: Effects of environmental change. Hormones and Behavior, 18, 206-215.

Priest, G. M. (1991). Training a diabetic drill (Mandrillus leucophaeus) to accept insulin injections and venipuncture. Laboratory Primate Newsletter, 30 (1), 1-4.

Priest, G. M. (1990). The use of operant conditioning in training husbandry behavior with captive exotic animals. Proceedings of the National American Association of Zoo Keepers Conference, 16, 94-108.

Public Health Service (1994). The importance of animals in biomedical and behavioral research. Laboratory Primate Newsletter, 33 (4), 12.

Public Health Service (1996). U.S. Government Principles for the Utilization and Care of Vertebrat Animals Used in Testing, Research, and Training. In National Research Council, Guide for the Care and Use of Laboratory Animals (pp. 117-118) Washington: National Academy Press.

Reichard, T., & Laule, G. E. (1993). Behavioral training of primates and other zoo animals for veterinary procedures. Proceedings American Association of Zoo Veterinarians, 65-69.

Reichard, T., & Shellaberger, W. (1992). Training for husbandry and medical procedures. American Zoo and Aquarium Association (AZA) Annual Conference Proceedings, 396-402.

Reinhardt, V. (1991). Training adult male rhesus monkeys to actively cooperate during in-homecage venipuncture. Animal Technology, 42, 11-17.

Reinhardt, V. (1992). Improved handling of experimental rhesus monkeys. In H. Davis, &A. D. Balfour (eds), The Inevitable Bond. Examining Scientist-Animal Interactions (pp. 171-177) Cambridge: Cambridge University Press.

Reinhardt, V. (1998). Methoden zur Belastlungsminderung bei Rhesusaftten (Macaca mulatta) im Versuchslaboratorium. Der Tierschutzbeauftragte, 7, 24-28.

Reinhardt, V., & Dodsworth, R. (1989). Facilitated Socialization of Previously Single Caged Adult Rhesus Macaques (Videotape with accompanying text). Madison: Wisconsin Regional Primate Research Center.

Reinhardt, V., & Cowley, D. (1992). In-homecage blood collection from conscious stumptailed macaques. Animal Welfare, 1, 249-255.

Reinhardt, V., & Reinhardt, A. (2000). Environmental Enrichment for Caged Rhesus Macaques (Macaca mulatta): Photographic documentation and literature review (Web site).

Reinhardt, V., & Reinhardt, A. (2000). Social enhancement for adult nonhuman primates in research laboratories: A review. Lab Animal, 29 (1), 34-41.

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.

Robbins, D. Q., Zwick, H., Leedy, M., & Stearns, G. (1986). Acute restraint device for rhesus monkeys. Laboratory Animal Science, 36, 68-70.

Rosenblum, I. Y., & Coulston, F. (1981). Normal range of longitudinal blood chemistry and hematology values in juvenile and adult rhesus monkeys (Macaca mulatta). Ecotoxicology and Environmental Safety, 5, 401-411.

Russell, W. M. S., & Burch, R. L. (1959). The Principles of Humane Techniques. London: Methuen & Co.

Scallet, A. C., McKay, D., Bailey, J. R., Ali, S. F., Paule, M. G., Slikker, W., & Rayford, P. L. (1989). Meal-induced increase in plasma gastrin immunoreactivity in the rhesus monkey (Macaca mulatta). American Journal of Primatology, 18, 315-319.

Schnell, C. R. (1997). Haemodynamic measurements by telemetry in conscious unrestrained marmosets: Responses to social and non social stress events. In C. Pryce, L. Scott, & C. Schnell (ed), Marmosets and Tamarins in Biological and Biomedical Research (pp. 170-180). Salisbury: DSSD Imagery.

Schnell, C. R., & Wood, J. M. (1993). Measurement of blood pressure and heart rate by telemetry in conscious, unrestrained marmosets. American Journal of Physiology, 264, H1509-1516.

Schultea, T. D., & Stein, F. J. (1981). A simple restraining device for small primates. Lab Animal, 10 (5), 67-69.

Streett, J. W., & Jonas, A. M. (1982). Differential effects of chemical and physical restraint on carbohydrate tolerance testing in nonhuman primates. Laboratory Animal Science, 32, 263-266.

Suleman, M. A., Njugana, J., & Anderson, J. (1988). Training of vervet monkeys, sykes monkeys and baboons for collection of biological samples. Proceedings of the XIIth Congress of the International Primatological Society, 12.

T-W-Fiennes, R. N. (1972). Primates – General. In Universities Federation for Animal Welfare (ed), The UFAW Handbook on the Care and Management of Laboratory Animals Fourth Edition (pp. 374-375). London: Churchill Livingstone.

Tatoyan, S. K., & Cherkovich, G. M. (1972). The heart rate in monkeys (Baboons and Macaques) in different physiological states recorded by radiotelemetry. Folia Primatologica, 17, 255-266.

Traystman, R. J. (1987). ACUC, who needs it? The investigator's viewpoint. Laboratory Animal Science, 37 (Special issue), 108-110.

Valerio, D. A., Miller, R. L., Innes, J. R. M., Courtney, K. D., Pallotta, A. J., & Guttmacher, R. M. (1969). Macaca mulatta – Management of a Laboratory Breeding Colony. London: Academic Press.

Verlangieri, A. J., De Priest, J. C., & Kapeghian, J. C. (1985). Normal serum biochemical, hematological, and EKG parameters in anesthetized adult male Macaca fascicularis and Macaca arctoidesLaboratory Animal Science, 35, 63-66.

Vertein, R., & Reinhardt, V. (1989). Training female rhesus monkeys to cooperate during in-homecage venipuncture. Laboratory Primate Newsletter, 28 (2), 1-3.

Wall, H. S., Worthman, C., & Else, J. G. (1985). Effects of ketamine anaesthesia, stress and repeated bleeding on the haematology of vervet monkeys. Laboratory Animals, 19, 138-144.

Whitney, R. A., Johnson, D. J., & Cole, W. C. (1973). Laboratory Primate Handbook. New York: Academic Press.

Wickings, E. J., & Nieschlag, E. (1980). Pituitary response to LRH and TRH stimulation and peripheral steroid hormones in conscious and anaesthetized adult male rhesus monkeys (Macaca mulatta). Acta Endocrinologica, 93, 287-293.

Woolley, A. P. A. H. (1997). Requirements of biomedical research in terms of housing and husbandry for non-human primates: Pharmacology & Toxicology. Primate Report, 49, 37-41.

Yeoman, R. R., Williams, L. E., Hazelton, J. M., Ricker, R. B., & Abee, C. R. (1988). The effects of brief manual restraint, prior conditioning and Ketamine sedation on luteinizing hormone and estradiol levels in the female Bolivian squirrel monkey. American Journal of Primatology, 14, 454-455.

Reproduced with permission of Lawrence Erlbaum Associates 
from Journal of Applied Animal Welfare Science 3(4), 321-333 (2000).


Share This!