Selection of an animal model is one of the most important steps in any of the experimental pharmacological study. Animal model preferred for the study must be producing similar disease profile as in the human.

1. ANIMALS USED IN
PHARMACOLOGICAL
EXPERIMENTS
SIVASWAROOP YARASI

2. INTRODUCTION:
• Selection of an animal model is one of the most important steps in any of the
experimental pharmacological study.
• Animal model preferred for the study must be producing similar disease profile
as in the human.
• Suitable animal model should be selected which follows three main objectives:
• Use of an animal phylogenetically closer to man or
• Use of an animal in which the process under investigation is as close as
possible to that in man,
• The Anatomy, Physiology and Biochemistry are considered to be similar

3. Broadly experimental animals are divided into three categories.

4. Rodents

5. Mouse as an
Experimental
Animal (Mus
musculus)
• In the biomedical research mice are
preferred which are the smallest rodents
used in the laboratory.
• Several advantages over other species like
• They are easy to keep, handle and
• require small place for housing.
• Invaluable resource in identifying the
several alleles which further develop in the
research of mutagenesis.
• Only known species in which it is possible
to grow totipotent embryonic stem (ES) cells
in vitro, and can form germ line once re-
injected into a developing embryo.

6. • DBA/2 is the most ancient of all
in bred strains, established by
CC Little in 1909 whereas
C57BL/6 was established by
Miss Lathrop after 10 years.
• Other commonly used strains
C3H, CBA and A were
discovered by LC Strong.
• Common diseases:
salmonellosis like mouse
typhoid, small pox,
streptobacillus infection.

7. • Due to the large similarity in mice and human genome (>99% conserved), it provides
good model for research not only on mammalian biology but also on a wide variety of
human diseases like, cancer, diabetes, ageing, atherosclerosis, immunological disease,
autoimmune disorders, neurological dysfunction and other endocrine diseases and
several other diseases.
• Knockout and Knock in mice have been developed for the selective assessment at the
genetic level.
• Knockout mice: Selective gene is taken out
• The first knockout mouse was created by Mario R Capecchi, Martin Evans and
Oliver Smithies in 1989, for which they were awarded the Nobel Prize for Medicine in
2007.
• Knock in mice: gene of interest is introduced.
• In 2006, Nobel Prize was awarded to Andrew Z. Fire and Craig C Mello for RNA
interference, in which genes are silenced or “knocked down” by short pieces of double
stranded RNA.

8. • Uses: acute toxicity studies, insulin assay, chemotherapeutic and teratogenic
agents screening, cancer and genetic research, isolated preparations- vas
deference, ileum

10. Rat as an
Experimental
Animal
(Rattus
norvegicus)
• Most commonly used animal in the biomedical research.
• “Wistar rat” and the “Sprague Dawley rat” are preferred
because of easy handling, sensitivity and low cost.
• The Albino rat (officially known as the Pink-Eyed White or
PEW) is most likely the very first mutation to be discovered
and purposely bred.
• Nude rats resemble nude mice in their lack of a normal
thymus and functionally mature T cells and are phenotypically
hairless with possible fine-sparse hair growth and most
preferred model in immunological research.
• Rat is preferably used in the research of behavior,
pharmacology, physiology, neurosciences, immunogenetics,
transplantation, cancer risk assessment, cardiovascular
diseases and aging.

11. • Uses: evaluation of psychopharmacological
agents, toxicity studies, antiulcer agents, liver
physiological studies, antihypertensive
effects, hormones assay.

13. Some important phenotypic differences
between baby rats and mice
• Baby rat has blunt and broad large head relative to body whereas
mice have triangular, small head relative to body
• Baby rat has small ears relative to the head whereas mice have
large ears
• In the baby rat hind paw and body ratio is larger as compared to
mice
• Tail is thick and shorter than body length in baby rat while mice
have thin and larger or same length tail as compared to body.

14. Guinea Pig
(GP) as an
Experimental
Animal
(Cavia
porcellus)
• 3 major varieties of strains used in the experimental studies
and is the member of rodents suborder “Hystricomorpha.
• herbivorous and eats green foods, seeds and roots
• it is essential to add vitamin C (Ascorbic acid) in the chow,
while it is important to note that GP are not able to synthesize
the required vitamin C daily.
• It is recommended that when GP is provided with the
greens, then ascorbic acid should be given at the rate of
1gm/L of drinking water on a weekly basis.
• If they are completely dependent on the chow then
vitamin C should be added in the dose of 200 mg/L daily.
• Duration of estrous cycle will range from 13-20 days an
average of 16 days can be further divided into the other
stages such as proestrus, estrus, metestrus and diestrus.

15. • It is sensitive to various diseases and
infections which makes it suitable for the
diagnostic tests.
• It is an ideal model for the enteric
amoebiasis and widely used in the
hypersensitivity, immune response,
anaphylactic shock, encephalomyelitis,
tuberculosis and ascorbic acid
metabolism.
• Also widely used in the screening of local
anesthetics and is good proposed model
for bronchial asthma, COPD.

16. • Used in evaluation of bronchodilators,
sensitization studies like egg albumin and
horse serum, study of local anaesthetics,
bioassay of digitalis, histamine and
acetylcholine, screening of spasmodic and
antispasmodic compounds.

17. Gerbil as an
Experimental
Animal
(Meriones
unguiculatus)
• Mongolian gerbil is a small laboratory rodent, having
length in between rat and mice.
• phenotypically related to rat and also known as “jirds”
or “sand rat”
• preferred in the
• laboratory because of ease in handling, mild and
• quiet nature
• Housing space of the gerbils are different at different
places such as in
• USA, it is said that 5 gallons (1 gallon = 231 cubic
inches) are required for each gerbil, i.e. 10 gallons
for 2 gerbil, 15 gallons for 3 gerbil, 20 gallons for 4
gerbil, etc.
• UK, for a pair of Gerbils a 15” by 12” by 10” tank is
ideal.

18. • Gerbil is widely used as a research animal in the field of stroke,
epilepsy, auditory studies (hearing curve similar to man),
parasite and bacterial infections and lipid metabolism and heart
disease studies (high serum cholesterol levels).
• This animal is one of the few species which were originally
developed in Japan as laboratory animals.

20. Hamster as
an
Experimental
Animal
(Mesocricetus
auratus)
• Hamster a brown to gold color animal has become
the third most commonly used laboratory
experimental animal in the biomedical research.
• They have different strainsnamely Syrian hamsters
(Golden), Chinese hamster (striped back), European
hamster and Armenian hamster (gray).
• Syrian hamster is the most commonly used in
biomedical research because of availability and ease
of reproduction.
• Relatively free from spontaneous disease and
susceptible to many introduced pathogenic agents.
• European hamster (quite larger than other hamster
species (300-400 gm)) is a more suitable model for
highly concentrated and prolonged smoke inhalation
studies than the Syrian hamster.

21. • Armenian hamster is more specific for the research to mutagenic
and carcinogenic agents and for studying meiosis due to its
susceptibility.
• Chinese hamster has the lowest number of chromosomes
compared to any other placental nurtured laboratory animal and it
is useful for cytogenesis research.
• Spontaneous model of human diseases such as diabetes mellitus,
Syrian hamster dystrophy (Autosomal recessive skeletal muscle
degeneration, cardiomyopathy, cardiohypertrophy, and congestive
heart failure), cholesterol cholelithiasis or gall stones, polycystic
diseases, dental caries.
• Good model for physiology and pathogenesis of Duchenne’s
dystrophy, variable sizes of muscle, fiber, centrally located nuclei,
with fatty infiltration and fibrous connective tissue replacement.

22. • Hamsters are used extensively in slow virus (Scrapie,
chronic measles, etc.) type C, Onco virus, influenza virus,
respiratory syncytial virus (RSV) studies and vaccine
production (Foot and Mouth).
• Due to anatomical advantages, cheek pouches do not have
intact lymphatic drainage and hence, they are an ideal site
for tissue transplants, such as, tumors and grafts.
• Hamsters are used for in vivo and in vitro diagnostic
techniques for numerous infectious agents (i.e. Clostridium
spp; Leptospirosis spp)

24. Non-rodents
(Mammalians)

25. Rabbit as an
Experimental
Animal
(Oryctolagus
cuniculus)
• Most common strain in use is New Zealand white
rabbit, followed by the Dutch, the Flemish Giant and
other minor strains of the domestic rabbit.
• New Zealand white rabbits have been used in the
screening of different drugs for diseases like diabetes,
diphtheria, tuberculosis, cancer, and heart diseases.
• Biomedical research studies in which rabbits is
commonly used are genetics, nutrition, toxicology,
physiology, immunology and reproduction.
• Classically the rabbit has been utilized in human
medicine to determine pregnancy in women by injecting
the serum from the patient into the rabbit and thereby
inducing ovulation in the doe.
• Apart from the drugs, effects of skin creams, cosmetics,
special diets, and food additives have also been tested
on New Zealand white rabbits.

26. • Other important uses are:
• Standard animal for pyrogen testing of all solutions for human medical use
• To test toxic effects of cosmetics and pharmaceuticals
• Good model for the production of antibodies and antiserums.
• New Zealand white rabbits have a genetic deviation called albinism. Albinism is
caused by ack of melanin.
• Rabbit is homologous to humans to react similarly to diseases and medications.
• A female rabbit (doe) is fertile all year long.
• The gestation period is around 28 to 31 days.
• Cervical dislocation which is generally preferred for the rodent is not suitable for the
rabbit because of short neck.
• It has very simple cardiac conductive tissue, free of connective tissue and is an animal
of choice for many cardiac studies

29. Monkey as
an
Experimental
Animal
(Macaca
mulatta)
• Monkeys are one of the most commonly used mammalian in
the experimental studies others in the cue are dogs and cats.
• The rhesus monkey (Macaca mulatta) commonly used is
found in the South Asia.
• Adult body weight is 10-12 kg for male and 8-10 Kg for
female.
• During the study animal can be maintained in the gang cages
(single or in group).
• The determined dimension for the cage is 24" × 30" × 30" for
single or individual housing and 28 ft × 10 ft for group housing
(8 female and 1 male may be maintained).
• Diet consists of 18-20% protein, 65-70% carbohydrates, 4-6%
fat, 4-5% crude fiber, minerals, and vitamins.
• Monkeys are widely used as primate model to study drug
metabolism because they generally show a metabolic pattern
similar to humans.

32. Dog as an
Experimental
Animal
(Canis
familiaris)
• After monkey, dog is the most preferred advantages
being small alimentary tract and easily get trained
• Mongrel and Beagles are the most preferred for the
experiment purpose due to manageable size, moderate
length of hair coat, docile nature and ease to handle.
• Cardiovascular research is preferred in the dogs.
• Drugs acting on blood pressure and vascular system
are preferably screened.
• It is also a good model for diabetes mellitus and
reproduction.
• The dog is frequently used as a model for many human
conditions in areas such as cardiovascular research,
diabetes mellitus, ulcerative colitis, open heart surgery,
organ transplantation, central nervous system (CNS),
safety pharmacology and toxicology.

35. Cat as an
Experimental
Animal
(Felis catus)
• Cat has similar physiological features which are
common with humans than the laboratory rabbit
or rodent, hence they have been extensively
used in cardiovascular (CVS), behavioral and
biomedical research.
• Useful models in studying the transmission of
vitamins and minerals to the fetus and new
born.
• Cat has distinct nictiating membrane hence
commonly used in the screening of ganglion
blocking drugs.
• It is not a good model in the experiment on the
loss of righting reflex, because it regain its
righting reflex even fall from a high altitude.

36. • Cats are mainly used in the field of behavioral studies, cardiovascular
studies, nerve impulse transmission.
• e.g. reflexes of the respiratory system and spinal system, reflexes
associated with nociception, light perception, sound perception and
body reaction to exposure to chemical stimuli.
• Additionally, it is also used in the neuropharmacology (particularly the
testing of psychotropic drugs), toxicology, oncology and chromosomal
abnormalities studies.

38. Pig as an
Experimental
Animal
(Sus scrofa
domestica)
• Several isolated organ models, investigation of skin
permeation and for digestive systems, etc. are few important
areas of research with pig as an experimental animal.
• Preferred because, it is small sized at maturation as well as is
selecting for less hair contains on the body
• In Europe, pigs are used in pharmaceutical R & D studies in
place of dogs and primates.
• Dissimilarities are in the vascularization (rich in man, poor in
the pig) and in the sebaceous glands.
• Humans have mostly eccrine sweat glands over the body
surface, whereas the pig has only apocrine glands.
• Similar findings also observed while studying the skin of other
domestic mammals.
• Pig has small lungs in relation to body size and is susceptible
to bronchitis and pneumonia.

40. Zebra Fish
(Danio rerio)
• Dr George Streisinger at the University of Oregon observed
that the Zebra fish is a suitable model for studying vertebrate
development and genetics in early 1970’s and is considered
to be the “Father of Zebra fish research”
• Zebra fish are vertebrates and have a backbone like humans
which gives more close relation to humans than commonly
used invertebrate models, such as insects and worms
• Studying embryo development and genetics make it useful
animal model as in genetic techniques.
• Due to its clear eggs which can be developed outside the
mother’s body and allow watching a zebra fish egg grow into
a newly formed fish under a microscope in 2-4 days it got
popular.
• The lifespan of zebra fish is considered to be approximately 5
years and length of the adult fish is about 6 cm.

41. • It can be kept at fairly high densities in a small tank, so it is cheaper to maintain than
other experimental animals,
• A single spawning produces 100-200 eggs which are easily collectible,
• Development of eggs is clear and easily observed and manipulated
The advantages of this model is that
• It requires an aquarium to maintain,
• Not closely related to humans as a mouse or other animal model (not mammalian) and
• Genetic modification has not been possible as it is in the mouse (Knock out/Knock in).
Drawbacks are

43. Character Mice Rat Guinea pig Hamster Gerbil Rabbit
Scientific name Mus musculus Rattus norvegius Cavia porcellus Mesocricetus
auratus
Meriones
unguiculatus
Oryctolagus
cuniculus
Weight (g) 18-40 150-400 600-1200 85-150 55-100 1000-3500
Life span (year) 1.5-3 2-4 4-8 1-3 2-4 6-12
Gestation period (days) 19-21 21-23 59-72 15.6-16 24-26 31-32
Estrous cycle (days) 4-5 4-5 15-19 4 4-6 5-14
Rectal temperature (°C) 38-39 36-40 37.2-40 37-38 37-38.5 38.5-40
Heart rate (min) 310-840 250-450 230-380 250-500 360 130-325
Blood pressure 133-160/90-110 84-134/60 80-94/55-58 150/100 90-130/60-90
Blood volume (ml/kg) 58.5 54-70 69-75 78 66-78 57-65
Respiratory rate 60-220 70-115 42-104 35-135 90 30-60
Mating age 6-8 weeks 10-12 weeks 12-20 weeks 6-8 weeks 3 months 6-9 months

44. References:
• Medhi B, Prakash A. Practical manual of experimental and clinical
pharmacology. Jaypee Brothers Medical Publishers; 2010.