Happy animals make good science

Trevor Poole
Universities Federation for Animal Welfare, 8 Hamilton Close, Potters Bar, Hertfordshire EN6 3QD, UK

Summary
In this paper the question is posed whether it is not only better for the animal to be happy, but
whether its state of mind may also have the potential to influence the scientific results
derived from it. To ensure good science, the animal should have a normal physiology and
behaviour, apart from specific adverse effects under investigation. There is a growing body of
evidence from a wide variety of sources to show that animals whose well-being is
compromised are often physiologically and immunologically abnormal and that experiments
using them may reach unreliable conclusions. On scientific, as well as ethical grounds,
therefore, the psychological well-being of laboratory animals should be an important concern
for veterinarians, animal technicians and scientists.

Keywords Well-being; laboratory animals; endocrine; immune response; handling;

experimental method

What are happy animals?
Most people who have worked closely with
animals or who keep them as pets are aware
if they are suffering or unwell; the signs may
be small but we become aware that all is not
well. Colloquially, we will say to our
colleagues 'that animal is not happy'. The
signs which tell us that there is something
wrong are changes in the behaviour which
we have come to expect from the individual,
for example, we may find it sitting huddled
in a comer, failing to greet us or lacking
interest in events taking place around it. If
the behavioural change persists, we take
action and may even call in veterinary
advice.
Happiness and unhappiness, or distress,
refer to states of mind of the animal; they
cannot be measured directly but the whole
concept of animal welfare is based on the
belief that higher animals, like us, are able to
experience pain and pleasure. The best way
to decide whether an animal is happy or
distressed is by observing its behaviour. On
Corespondence to: Trevor Poole
this basis, I will define a 'happy animal' as
one which is alert and busy (shows a wide
repertoire of behaviour), is able to rest in a
relaxed manner, is confident (outward going
and does not display fear towards trivial non-
threatening stimuli) and does not show
abnormal behaviour. It is, of course, impor-
tant to be familiar with the particular
.animal's character to make these judge-
ments. Some individuals are naturally
extrovert and active, while others are quiet
and lethargic. In the laboratory, those of us
who care for animals like to think that our
charges are happy and that any procedures
which have to be performed on them cause
them the absolute minimum of distress.
In this article the question is posed
whether it is not only better for the animal to
be happy, but whether its state of mind may
also have the potential to influence the
scientific results which are derived from it.
The most obvious cases of unhappiness will
occur when animals are sick or injured and
symptoms will vary from mild to severe.
Generally, with modem laboratory practice
this source of distress has virtually been
eliminated. We take it for granted that

Accepted 6 September 1996 LaboratoryAnimals (1997) 31,116-124

Happy animals make good science
scientists do not work with animals which
are ill or injured. Nor do laboratory animals
lack essential physical needs, such as food,
water or suitable climatic conditions. There
remain, however, a variety of potential
causes of distress, such as social problems
with aggressive cage mates, overcrowding, or
social isolation. There are also features of the
physical environment, such as loud or
sudden noises, including ultrasound which
can be perceived by rodents, dogs and smaller
primates, which might also be sources of
distress. Finally, there are the attitudes and
sometimes inexpert manipulations by staff.
Mammals, particularly become distressed if
they are badly handled, especially when they
are restrained by personnel unfamiliar to
them. This may be a common occurrence, as
the experimenter is not usually the person
in day-to-day care. A factor which is
increasingly being recognized as a source
of unhappiness, is the failure of the captive
environment to meet the animal's
behavioural needs and assure its psycho-
logical well-being. It is becoming apparent
that captive mammals can be bored or resort
to abnormal behflviour if their environment
is not sufficiently complex and interesting to
them (Wemelsfelder 1990, Poole 1988).
What is good science?
The quality of experimental laboratory ani-
mal science depends on three essential
conditions being satisfied. Firstly, there
should be an important problem for which an
answer is sought, secondly, the experiment
should yield unambiguous results which
provide an answer to the problem and,
finally, variables which are not under in-
vestigation should be strictly controlled. I
shall take for granted the assumption that the
first two conditions have been met and only
be concerned with the third which, can also
have a direct bearing on the well-being of the
animals. Good laboratory animal science is
based on normal, healthy subjects, unless the
illness is itself the subject of investigation.
Scientific method assumes the absence of
confounding factors or uncontrolled vari-
ables. Clearly, unhappiness might be a
confounding variable unless, for example, its
117
alleviation was the subject of the study, as in
the case of testing an anti-depressant. What-
ever the subject under investigation, all
unnecessary stress should be minimized
during the experiment to reduce the varia-
bility of the results and thus the number of
animals required. This requires, firstly, a
thorough understanding of the animal and its
biology and, secondly, experiments which are
well designed, statistically valid and appro-
priate. Even in situations where the experi-
ment itself creates unhappiness for the
animal, such as premature removal of young,
any effect may be diminished or even lost if
the animal was not happy in the first
instance. We can therefore conclude that, in
all aspects, apart from unavoidable adverse
effects of the experiment, the animal should
be happy.
Most scientists working with animals will
make the assumptions that they will have
normal blood pressure, heart rates, levels of
stress hormones, immunological compe-
tence, digestion, appetite and behaviour. To
avoid confounding variables, experimental
animals should have both normal physiology
and behaviour. Some might argue that
behaviour is of less significance than phy-
siology, but this is based on the erroneous
supposition that mind and body are separate
entities and that one will not influence the
other. Recent scientific work has shown how
the brain, behaviour, hormones and even the
immune system, are all interdependent and
that disturbances in one of these systems
commonly influences one or all of the others
(see review article by Martin 1989 and Bohus
& Koolhaas 1991).In fact, behavioural
changes are usually more sensitive indicators
of distress than physiological ones. I shall
now consider some of the main factors which
may influence the psychological well-being
of laboratory animals.
Factors influencing psychological
well-being
Social factors
Laboratory mice are commonly kept in single
sex groups in stock cages. While females
generally tolerate such conditions, males
118
fight and establish a hierarchy, but the type
of social structure depends on the number of
individuals in the cage. Poole and Morgan
(1973) found that, in small colonies of 3--4
male CFW mice, the dominant's aggression
was directed to few rivals and these sub-
ordinates were highly intimidated and re-
stricted in their movements about the cage.
Five male mice however formed a linear
hierarchy with each individual knowing its
place and thus subordinates were able to
develop strategies to avoid conflict. In larger
colonies of nine or more individuals the
dominant was unable to control such a large
number of subordinates, so that the social
structure broke down after 3-5 days and
another dominant arose. This contrasted
with the situation in smaller groups of up to
five in number where, barring disturbance,
aggression gradually decreased and was
minimal after 12-15 days. Physiological data
from laboratory mice have shown that, in
standard housing, subordinates exhibit high-
er levels of stress and sex hormones than
dominants (Hucklebridge et al. 1976, Benton
et al. 1978). In addition to experiencing fear,
suffering injury and high levels of stress
hormones, Beden and Brain (1984, 1985)
found that the immunological response to an
antigen (sheep red blood cell) was reduced in
subordinate or defeated mice. Brayton and
Brain (1973) found that crowding mice
lowered their resistance to a digenean para-
site and Edwards and Dean (1977) also
showed that crowding affects the mouse's
immune response.
Age is another important consideration
when housing male micej litter mates, unless
significantly disturbed will usually live
amicably together, as will members of
different litters who have been grouped
together from an early age. Clearly, wherever
possible, animals, should be kept in condi-
tions where their social grouping leads to the
minimum of aggression, and hence distress.
There has been a tendency to believe that
isolation in the form of single housing is
distressing for other mammals, as it is for
humans. However, it has been found that
isolated male mice have hormonal profiles
similar to dominants (Brain 1975, Huckle-
bridge et al. 1976, Brain & Benton 1977,
Poole
Benton et al. 1978, Brain 1990), so that
singly-housed mice do not suffer from 'iso-
lation stress'. This finding is compatible with
the fact that mice are territorial in the wild
and thus actively repel other males. How-
ever, providing a simulation of the wild in
the laboratory may actually be deleterious
because Bishop and Chevins (1988) found
that territorial male mice placed in an arena
had high levels of stress hormones, presum-
ably associated with the defence of their
territories. While access to social compa-
nions benefits many species of laboratory
animals, some solitary species, may have to
be kept alone because of their aggressive
tendencies, for example, male rabbits and
ferretsj this is particularly common in cases
where males have bred or been exposed to
members of the opposite sex, or females have
infant young. Even individuals of social
species must have adequate space to avoid
one another and thus minimize any conflict.
Bohus and Koolhaas (1991) reviewed the
literature on psycho-immunology and came
to the conclusion that social stress is only
likely to impair immune function signifi-
cantly when the animal is unable to exert
some control over the situation by develop-
ing a coping strategy. Inability to escape from
an attacker and chronic overcrowding are
clear examples of situations which animals
are unable to control.
It is important to remember that a rat is
not simply a scaled-up mouse. Rats are much
more sociable than mice and consequently
seem likely to suffer more when isolated,
although Brain and Benton (1979) could find
no evidence of isolation stress in this species.
However, young rats show very active social
play which involves both chasing and wrest-
ling (Poole & Fish 1975, 1976), so they need
adequate space to do this. During their
developmental stage, rats acquire skills and
experience; adult rats reared in deprived
conditions are not only less intelligent, but
also have smaller brains than those from rich
and stimulating environments (Renner &
Rosenzweig 1978). They are thus less normal,
but this does not necessarily mean that they
are less happy.
Beynen (19921 reviewed literature which
indicated that control rats in the same room
Happy animals make good science
as the experimentals showed raised levels of
corticosteroids, as compared to controls in
another room. This suggests that some rats
(and therefore possibly other animals) may be
able to communicate their feelings to other
individuals either by vocalizations or pher-
omones and that situations which cause
distress may also upset others within the
range of these forms of communication.
Mendoza et a1. (1991)found that squirrel
monkeys showed differences in levels of
corticosteroids which related to their sex and
social grouping. Females showed higher
levels when kept singly, with a single female
companion, or with a male. Three females
housed together appeared to be the minimum
social group which would reduce the levels of
corticosteroids to a normallevelj this num-
ber also showed much higher levels of
reproductive cycling as compared to the
smaller groups or females paired with a male.
Likewise male squirrel monkeys showed
lower levels of corticosteroids when housed
with male companions. The practical im-
plication for husbandry and breeding is that
the minimum breeding group should consist
of two males and three females.
Both mammals and some birds have a
period of life when they acquire knowledge
of the world and are able to test its proper-
ties while protected by a vigilant mother or
family group. The developmental environ-
ment determines, to a large extent the kind
of situations with which they are able to
cope when they reach adulthood. During
childhood they practise skills and motor
coordinations which will be of benefit in
later life. Many mammals play fight when
young and thus practise the strategies of
attack and defence which they will need
when faced with real rivals. They show
extraordinary curiosity and inventiveness
and thus learn the properties of objects and
other organisms in their environment.
Mammals enjoy play and experimentation in
the sense that it is self-rewarding, so that
they should be provided with a stimulating
and complex developmental environment.
Likewise, the presence of a mother is
important because it allows the young to
express their wide repertoire of play and
curiosity without fear.
119
Early weaning is undoubtedly stressful for
mammals because of the upset caused by
losing their mothers. The problem is further
exacerbated by the sudden loss of maternal
antibody. This immune deficiency is tem-
porary until the young independent animal
develops its own fully functioning immune
system. However, the temporary immuno-
deficiency may be enhanced by stress result-
ing from separation and immuno-suppression
has been recorded from both adult pigs
(Blecha & Kelley 1981, Blecha et a1. 1983)and
primates (Reite 1987)which had been re-
moved from their mothers unnaturally early.
For example, Reite showed that the separa-
tion of young Macaca nemestrina for 2 weeks
at the age of 6 months still had an effect on
the immune system in the form of a
reduction in T-cell proliferation in response
to a mitogen 6 years later. Early separation
from the mother, is commonly practised by
the breeders of non-human primates, so that
the young not only develop abnormal beha-
viour (Goosen 1989)but may also suffer from
reduced immunological competence as
adults, and thus, would be unsatisfactory as
experimental animals.
The phYSical environment
There is increasing evidence that a number of
physical environmental factors which influ-
ence an animal's psychology may also affect
its immune system. Unpleasant events, such
as inescapable electric shock, increase the
incidence of tumours in rats (Keller et a1.
1981).However, not all stress is deleterious
and some may even be beneficial. For
example Marsh et a1. (1963)found that
cynomolgus monkeys (Macaca fascicularis)
trained over a 24-h period to avoid electric
shocks increased resistance to polio virus
infection. Similarly, mice which had been
trained to avoid electric shocks showed
greater resistance to malaria than controls
not subjected to the training. What seems to
be important in these animals is not the
shock itself but the degree of control which
the animal is able to exert to avoid it.
Mice conditioned to drink saccharine
solution followed by an immuno-suppressive
drug (cyclophosphamide) were subsequently
120
found to have a suppressed immune system
when drinking saccharine alone. This indi-
cates that the immune response may actually
be susceptible to Pavlovian conditioning
(Kelley et a1. 1984, 1985).
Differences in levels of stress hormones
also relate to the animal's ability to control
events. Rats were subjected to an electric
shock from the grid on which they walked.
Where the rat could prevent the grid from
becoming electrified by pressing a lever,
corticosteroid levels were much lower than
in controls which were shocked but had no
way of switching it off.
There are also marked species differences
in responsiveness to stressors, even when
they are closely related, for example rhesus,
bonnet and cynomolgus macaques show
marked differences in hormonal responses to
routine procedures (Clark et a1. 1988).
Mendoza and Mason (1984) compared the
physiology of titi (Callicebusl and squirrel
monkeys (Saimiri). The former are notor-
iously difficult to keep in the laboratory
whereas squirrel monkeys readily adapt to
captivity. The two species show very differ-
ent endocrinological responses to stress.
Interestingly, Callicebus shows very limited
corticosteroid response to stress compared to
Saimiri and the authors suggest that the
capacity to show a high level of cortico-
steroids relates to the lifestyles of the
two species. Saimiri is an active, mobile
and highly exploratory species.whereas Cal-
licebus has a small home range, is mono-
gamous and leads a rather quiet life. Thus in
keeping species in captivity it is important to
consider their ability to adapt to an artificial
environment which is far removed from their
natural way of life. The titi monkey is clearly
unhappy in captivity and has only a limited
ability to cope with a profound change from
its natural environment.
Mild unpredictable stressors (such as water
deprivation, continuous illumination, cage
tilt, living in a soiled cage, or loud noises)
have been shown to influence the appetite of
rats and mice for sweet substances (Willner
et a1. 1987, Monleon et a1. 1995). These
uncontrolled variables, which may be asso-
ciated with poor husbandry, could seriously
compromise experiments using a food re-
Poole
ward. Exposure to bright light, often resulting
from cages being high on a rack, can also be
aversive to nocturnal rodents and can induce
retinal degeneration, prenatal mortality and
decreased growth rates in various strains of
rats and mice (Clough 19841.Schlingmann et
a1. (1993) showed that rats show avoidance
behaviour to light intensities as low as
20-25 lux, which is well below the threshold
for retinal degeneration (60 lux). In many
instances experiments on rats and mice are
carried out during the daytime and in bright
light, when the animals would normally be
asleep. This would seem certain to cause
them some distress but, as far as I am aware,
no one has investigated whether such con-
ditions may add to any stress caused by the
experiment.
The environment may also contain stres-
sors of which we are unaware. An obvious
example is noise which is in the ultrasonic
range and can be perceived by and is known
to influence the behaviour of rodents. I recall
entering an experimental laboratory where
drugs were tested on rodents. It contained
five computers with visual display units.
Such equipment emits a high pitched ultra-
sonic scream which is almost indistinguish-
able from the fear cry of a rat (Sales et a1.
1988). Three computer visual display units
(VDUs) were switched on when I entered the
laboratory and, when I asked whether the
computers were switched off during experi-
ments, the scientists were obviously sur-
prised by my question and unaware of the
possibility that VDUs might affect experi-
mental results!
Some of the most stressful events in every
day husbandry result from changes in envir-
onment. Animals may be placed in unfami-
liar/ clean cages and, for mammals which
scent mark their home range, this may be
highly disturbing. For example, rodents often
fight when moved to another cage. Even
more stressful is the situation where an
animal is moved from its home cage to an
unfamiliar one and then subjected to an
experiment. It is good practice to allow
plenty of time for the animal to acclimatize
to its new situation, not only on welfare
grounds but also because the experimental
results may be influenced. For example
Happy animals make good science
Damon et a1. (1986) compared the nephro-
toxic response of rats to implanted, refined
uranium ore. They implanted group I rats and
then moved them to metabolism cages; group
II was allowed 21 days to acclimatize to the
metabolism cage before implantation, while
group III were housed in polycarbonate cages
and implanted after 21 days, four being
retained without implantation, as controls.
The surprising result was that, for group I
rats 3-8 mg/kg proved toxic, while for the
acclimatized experimental rats in groups II
and III, the toxic dose was 220-650 mg/kg.
This example provides concrete data to
support the practice of carrying out experi-
ments in a familiar environment.
Handling and training
Another important consideration which can
affect their well-being, is the way in which
animals are handled or restrained. Barclay et
a1. (1988) found significant values of their
'Disturbance Index' resulted from longer
periods of restraint lover 20 s) while Blecha et
a1. (1982) showed that mice restrained in a
wire cone for 2 h, had increased levels of
corticosteroids and that their immune re-
sponse was suppressed.
Barclay et a1. (loc cit) found that mice
showed significant Disturbance Indexes
when the handler had previously contacted
cat urine. Mice exposed to a cat (Hamilton
19741, or those which had been fighting, both
had lower levels of resistance to tapeworms
indicating a stress-induced immunosuppre-
sion.
It is well known that restraint can be
highly stressful to mammals (Cronin 1985,
Lawrence 1991) and it may also lead to
suppression of the immune system (Ras-
mussen et a1. 1957, Levine et a1. 1962). In
spite of this, in many laboratories monkeys
are manhandled, restrained in crush cages or
even anaesthetized to carry out even trivial
procedures such as injections or blood sam-
pling. Monkeys, like most mammals, can
easily be trained to cooperate in procedures.
For example, rhesus monkeys trained to
extend an arm for an injection showed a
much lower incidence of diarrhoea as com-
pared with animals who were physically
121
restrained IReinhardt 1990, 1992). Monkeys
in zoos have been trained to perform a variety
of tasks, for example, female drills were
encouraged to present for artificial insemi-
nation and a male to masturbate in a special
area to facilitate the collection of sperm.
Reinhardt (1991, 1992) also found that the
home cage is the best place to carry out
venipuncture on Macaca nemestrina and
that cortisol levels were lower in animals
trained to accept this procedure when
compared with individuals who were re-
strained. Monkeys can also be trained to open
their mouths for dental examination.
Most, if not all, laboratory mammals and
birds recognize humans as individuals and
are nervous of strangers. When an experi-
mental procedure is to be carried out it is
therefore preferable that the handler should
be a person familiar to the animal, in whom
it has confidence. An unfamiliar handler will
undoubtedly cause the animal fear and stress.
Wherever possible, laboratories should en-
sure that the animal is familiar with those in
direct contact with it during the experiment.
Thus, the role of the animal technician is of
vital importance and should be appreciated
by the scientist (Biological Council 19921.
Kind and gentle handling make all the
difference to the animal. This is referred to as
'stockmanship' in farming circles, where it
has been shown that a friendly stockman can
increase the milk yield of cows as compared
with persons who treat them humanely but
do not form any relationship with their
animals (Seabrook 1984). Atherosclerosis is
reduced in rabbits handled in a consistent
and friendly way as opposed to the more
usual laboratory procedure of simply picking
them up and restraining them (Nerem et a1.
1980). Good handling and friendly ap-
proaches have been shown to lead to greater
growth rates and reproductive success in pigs
(Hemsworth & Barnett 1987). Insome
instances experimental pigs with catheters
did better than controls, probably because
they received more attention from staff
(Wiepkema 1990). Good handling and train-
ing animals to cooperate, not only improves
the quality of the relationship between carer
and animal, but also allows the animal to
exercise its intelligence. One of the major
122
problems in experiments with conscious
animals is the fear or anxiety which the
subject experiences. If the experimental
animal has been trained to cooperate and has
confidence and trust in the handler it will be
much less stressed and the experiment will
be much improved by the removal of this
unwanted variable. Thus a positive, caring
attitude by staff not only improves the well-
being of the animal but also makes it more
willing to cooperate in any procedures to
which it is subjected.
There are, of course sources of potential
stress even in the best run animal houses.
Husbandry procedures themselves can dis-
turb animals and, for example, the routines
which occur regularly may affect animals in
ways which are not apparent. Line et al.
(1989) found that during cage cleaning the
heart rate of rhesus monkeys increased and
remained significantly above normal for 2 h
afterwards. Thus, there could be considerable
effects on, for example, drug metabolism,
depending on the time of day in which the
animal was given the dose. Barclay et al.
(1988) showed that the behaviour of rats was
significantly disturbed when they were re-
strained by an inexperienced handler as
compared to an experienced one.
One of the referees rightly pointed out that
this paper seems to have a bias toward rats,
mice and non-human primates; this is
correct, but I do believe that it reflects the
coverage in the scientific literature. While it
would be surprising if other species of
mammal, and probably birds, were not
affected similarly, there is no doubt that
additional information on other laboratory
animals would be valuable.
Conclusions
Happy animals are busy, confident and
behave normally. They will not be in pain, or
distressed and should resist disease and
reproduce successfully. I have given exam-
ples which show that both the endocrine
condition and immunology of laboratory
animals, which experimenters may assume
to be normal, can be compromised by social
conditions, developmental history and stres-
sors in the animal unit or experimental
Poole
laboratory. One of the most important
aspects of the life of laboratory animals are
their relations with human handlers and care
givers on whom they are totally dependent.
Good, kindly treatment and simple humane
training are beneficial both in reducing stress
and in producing animals which are con-
fident, cooperative and easily handled; they
will also be the best subjects for scientific
investigation. While it has to be accepted
that no animal can live an entirely stress-free
life, what I have termed a happpy animal is
readily able to cope with the stressors to
which it is subjected. Unhappy animals have
to put up with distressing conditions beyond
their control which result in behavioural and
physiological disabilities such as perma-
nently raised levels of stress hormones or
reduced concentrations of sex hormones and
a compromised immune system; these un-
controlled variables make them unsuitable
subjects for scientific studies. These findings
make it obligatory for scientists to do every-
thing practicable to ensure the happiness of
laboratory animals if the quality of their
research is to be beyond reproach.
Acknowledgment I am extremely grateful to Dr
E. D. Williamson for her very helpful comments on
this manuscript, however, I alone take responsibility
for the opinions expressed therein.
References
Barclay RJ, Herbert WJ, Poole TB (1988) The Dis·
turbance Index: a behavioural method of assessing
the severity of common laboratory procedures on
rodents. UFA W Animal Welfare Research Report 2,
Potters Bar: Universities Federation for Animal
Welfare
Beden SN, Brain PF (1984) Effects of attack-related
stress on the primary immune responses to sheep
red blood cells in castrated mice. IRCS Medical
Science 12, 675
Beden SN, Brain PF (1985) The primary immune
responses to sheep red blood cells in mice of
differing social rank or from individual housing.
IRCS Medical Science 13, 364-5
Benton D, Goldsmith JF, Gamal-el Din L, Brain PF,
Hucklebridge FH 11978) Adrenal activity in isolated
mice and mice of different social status. Physiology
and Behaviour 20, 459-64
Beynen AC (19921 Communication between rats of
experiment-induced stress and its impact on ex-
perimental results. Animal Welfare 1, 153-9
Happy animals make good science
Biological Council (19921 Guidelines on the Handling
and Training of Laboratory Animajs. Potters Bar:
Universities Federation for Animal Welfare
Bishop ML, Chevins PFD (1988) Territory formation by
mice under laboratory conditions: welfare consid-
erations. In Laboratory Animal Welfare Research
Vol. 1 Rodents (UFAW, edl. Potters Bar: Universities
Federation for Animal Welfare, pp 25-48
Blecha F, Kelley KW (1981) Effects of cold and
weaning stressors on the antibody-mediated im-
mune response of pigs. Journal of Animal Science
53,439
Blecha F, Kelley KW, Satterlee DG (1982) Adrenal
involvement in the expression of delayed-type
hypersensitivity to SRBC and contact sensitivity to
DNFB in stressed mice. Proceedings of the Society
for Experimental Biology and Medicine 169, 257
Blecha F, Pollman DS, Nichols DA (1983) Weaning
pigs at an early age decreases cellular immunity.
Journal of Animal Science 56, 396
Bohus B, Koolhaas JM 119911Psychoimmunology of
social factors in rodents and other sub primate
vertebrates. In Psychoneuroimmunology (Ader R,
Felten DL, Cohen N, eds). San Diego: Academic
Press, pp 807-30
Brain PF 119751What does individual housing mean to
a mouse? Life Sciences 16, 187-200
Brain PF (1990) Stress in agonistic contexts in rodents.
In: Stress in Domestic Animals (Dantzer R, Zayan
R, eds). Dortrecht: Kluwer Academic,
pp 74-85
Brain PF, Benton D 119771What does individual
housing mean to a research worker? IRCS Journal of
Medical Science 5, 459-63
Brain PF, Benton D 119791The interpretation of
physiological correlates of differential housing in
laboratory rats. Life Sciences 24, 99-116
Brayton AR, Brain PF 119731Effects of 'crowding' on
endocrine function and retention of the digenean
parasite Microphallus pygmaeus in male and
female mice. Journal of Helminthology 48, 99-106
Clark AS, Mason W, Moberg G 119881Differential and
behavioral and adrenocortical responses to stress
among three macaque species. American Journal of
Primatology 14, 37-52
Clough G 119841Environmental factors in relation to
the comfort and well-being of laboratory rats and
mice. In: Standards in Laboratory Animal Man-
agement (UFAW, ed). Potters Bar: Universities
Federation for Animal Welfare, pp 7-24
Cronin GM (1985) The Development and Significance
of Abnormal Stereotyped Behaviour in Tethered
Sows (PhD Thesis). Netherlands: Agricultural
University of Wageningen
Damon EG, EidsonAF, Hobbs CH, Hahn F 119861 Effect
of acclimation on nephrotoxic response of rats to
uranium. Laboratory Animal Science 36,24-7
Edwards EA, Dean LM (1977) Effects of crowding mice
on humeral antibody formation and protection to
123
lethal antigenic challenge. Psychosomatic Medi-
cine 39, 19-24
Friedman SB, Ader R, Grota LJ (1973) Protective effect
of noxious stimulation in mice infected with rodent
malaria. Psychosomatic Medicine 35, 535-7
Goosen C (1989) Influence of the age of weaning on
the behaviour and well-being of rhesus monkeys.
In: Laboratory Animal Welfare Research: Primates
(UFAW, edl. Potters Bar: Universities Federation for
Animal Welfare, pp 17-22
Hamilton DR (19741 Immunosuppressive effects of
predator-induced stress in mice with acquired
immunity to Hymenolepsis nana. Journal of
Psychosomatic Research 18, 143-53
Hemsworth PH, Barnett JL (1987) Human-animal
interactions. The Veterinary Clinician of North
America 3, 339-56
Hucklebridge FH, Reid A, Benton D, Brain PF (1976) A
comparison of the levels of the adrenal catechola-
mines and aggession in isolated, dominant and
subordinate mice. IRCS Medical Science 4, 154
Keller SE, Weiss JM, Miller NE, Stein M (1981)
Suppression of immunity by stress: effect of graded
scries of stressors on lymphocyte stimulation in the
rat. Science 213, 1397
Kelley KW, Dantzer R, Mormede P, Salmon H,
Aynaud J-M (19841 Conditioned taste aversion
induces immunological suppression in the absence
of an immunosuppressive drug. Comptes Rendus
des Seances de l'Academie des Sciences Serie III
299, 123
Kelley KW, Dantzer R, Mormede P, Salmon H,
Aynaud J-M (19851 Conditioned taste aversion
suppresses induction of delayed-type hypersensi-
tivity immune reactions. Physiological Behaviour
34, 189
Lawrence A (1991) Introduction: the biological basis
of animals responses to handling. In: Practical
Animal Handling (Anderson RS, Edney A, eds).
Oxford: Pergamon Press, pp 1-13
Levine S, Strebel R, Wenk E1, Harman PJ 119621
Suppression of experimental allergic encephalo-
myelitis by stress. Proceedings of the Society for
Experimental Biology and Medicine 109, 294
Line SW, Morgan KN, Markowitz H, Strong S 119891
Heart rate and activity of rhesus monkeys in
response to routine events. Laboratory Primate
Newsletter 28, 9-12
Marsh JT, Lavender JF, Chang S5, Rasmussen AF
(1963) Poliomyelitis in monkeys: decreased sus-
ceptibility after avoidance stress. Science 140,
1414-15
Martin P (1989) Psychoimmunology: relations be-
tween brain, behaviour and immune function. In:
Perspectives in Ethology 8: Whither Ethology!
(Bateson PPG, Klopfer PH, edsl. New York: Plenum
Press, pp 173-214
Mendoza SP, Mason WA (1984) Rambuctious Saimiri
and reluctant Callicebus: systemic contrasts in
124
stress physiology. American Journal of Primatology
6,415
Mendoza SP 11991) Behavioural and physiological
indices of social relationships: comparative studies
of New World monkeys. In: Primate Responses to
Environmental Change (Box HO, ed). London:
Chapman & Hall, pp 311-36
Monleon S, D'Aquila P, Parra A, Simon VM, Brain PF,
Willner P 11995) Attenuation of sucrose consump-
tion in l11ice by chronic mild stress and its
restoration by imipramine. Psychopharmacology
117,453-7
Nerem RM, Levesque MJ, Comhill JF (1980) Social
environment as a factor in diet induced athero-
sclerosis. Science 208, 1475-6
Poole TB (1988) Normal and abnormal behaviour in
. captive primates. Primate Report 22, 3-12
Poole TB, Fish J (1975) An investigation of playful.
behaviour in Rattus norvegicus and Mus musculus
(Mammalia). Journal of the Zoological Society of
London 175, 61-71
Poole TB, Fish J 11976) An investigation of individual,
age and sexual differences in the play of Rattus
norvegicus IMammalia: Rodential. Journal of the
Zoological Society of London 179, 249-60
Poole TB, Morgan HDR 11973) Difierences in
aggressive behaviour between male mice (Mus
musculus) in colonies of different sizes. Animal
Behaviour 21, 788-95
Rasmussen AF, Marsh JT, Brill NQ 11957) Increased
susceptibility to herpes simplex in mice subjected
to avoidance-learning stress of Il~straint. Proceed-
ings of the Society for Experimental Biology and
Medicine 96, 183
Reinhardt V (1990) Avoiding undue stress: catching
individual animals in groups of rhesus monkeys.
Lab Anima119, 52-3
Reinhardt V (1991) Training rhesus monkeys to
actively cooperate during in-horne cage venipunc-
ture. Animal Technology 42, 11-17
Poole
Reinhardt V (1992) Improved handling of experimen-
tal rhesus monkeys. In: The Inevitable Bond:
Examining Scientist-Animal Interactions IDavis
H, Balfour AD, eds). Cambridge: Cambridge Uni-
versity Press
Reite M (19871 Infant abuse and neglect: lessons from
the primate laboratory. Child Abuse and Neglect
11,347-55
Renner MJ, Rosenzweig MR (19781 Enriched and
Impoverished Environments. Effects on Brain and
Behaviour. New York: Springer-Verlag
Sales GD, Wilson KJ, Spencer KEV, Milligan SR (1988)
Environmental ultrasound in laboratories and
animal houses: a possible cause for concern in the
welfare and use of animals. Laboratory Animals 22,
369-75
Schlingmann F, Derijk SHLM, Pereboom WJ, Remie R
(1993) 'Avoidance' as a behavioural parameter in
the determination of distress amongst albino and
pigmented rats at various light intensities. Animal
Technology 44, 87-96
Seabrook MF (1984) The psychological interaction
between the stockman and his animals and its
influence on performance of pigs and dairy cows.
Veterinary Record 115, 84-7
Wemelsfelder F (19901 Boredom and laboratory animal
welfare. In: The Experimental Animal in Biomedi-
cal Research. (Rollin BE, Kessel ML, eds). Boca
Raton: CRC Press
Wiepkema PR 119901Stress: ethological implica-
tions. In: Psychobiology of Stress (Puglisi-Allegra
S, Oliverio A, eds). Netherlands: Kluwer,
pp 1-13
Willner P, Towell A, Sampson D, Muscat R,
Sopholeous S (19871 Reduction of sucrose prefer-
ence by chronic mild stress and its restoration by a
tricyclic antidepressant. Psychopharmacology 93,
358-64