it describes the animals commonly used in experimental pharmacology

1. 1
Dr.K.Sathishbabu
IInd year PG
Department of Pharmacology
07.05.2020
EXPERIMENTALANIMALS

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OVERVIEW
• Introduction
• Classification
• Animals
• Summary
• References

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INTRODUCTION
To study the effect of newly developed drug
we need experimental animals for safety and
efficacy measurement
Selection of an animal model – most
important step in any experimental
pharmacological studies

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Objectives for selection of animal model ;-
Phylogenetically closer to man
The process under investigation is as close as
possible to that in a man
Anatomy, Physiology and Biochemistry are
considered to be similar

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Classification
1.Rodents :
Eg : Mouse, Rat, Guinea pig, Gerbil, Hamster etc.
2.Non - rodents :
Eg : Rabbit, Monkey, Dog, Cat, Pig etc.
3. Misellaneous :
Eg : Frog, Pigeon, Zebra fish, Chicken etc.

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MOUSE

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MOUSE (Mus musculus)
• Smallest laboratory animal
• Uniform bred, Cheap and easy to handle
• Sensitive to very small doses of substance
• Strains :
- Commonly used : Swiss Albino mice
- Other strains : DBA/2, Balb/C and C-57

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• Large similarity in mice and human genome –
provides good model for genetic studies
• Knock out mice :
selective gene is taken out from the mice
• Knock in mice :
gene of interest is introduced in the mice
• Knocked down – genes are silenced by pieces of RNA

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• Nude mice : Hairless genetic mutant which lacks
thymus gland – used for tissue immunity and
transplantational research
• Biege mice : lack of NK cells and are susceptible to
cancer – used for cancer studies
Biege miceNude mice

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Used in
1.Acute toxicity studies
2.Assay of Insulin and analgesics
3.Screening of chemotherapeutic and teratogenic
agents
4.Cancer and genetic research
5.Isolated preparation - Vas deferens, ileum

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RAT

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RAT (Rattus norvegicus)
• Most commonly used
• Small size ; greater sensitivity to most drugs
• Most standardized of all lab animals
• Very sturdy to withstand long periods of
experimentation under anaesthesia
• Common strains : Wistar & Sprague - Dawley rats

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• Wistar rats :
Moderately prolific strain ; resistant to infection
Low incidence of spontaneous tumors
Wide head; long ears; tail length < body length
• Sprague – Dawley rats :
More prolific ; rapidly growing; less resistant to
infection
Long & narrow head ; tail length = body length

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• Lack of vomiting centre, tonsils, gall bladder
• Strong LES ; Extremely diffuse pancreas
• Stomach – two parts (Secretory & Non secretory)
• Secretory part – continuous spontaneous secretion
• Coprophagic animals
• Rat uterus – inhibited by adrenaline
• Physiologically, 24 hr old rat = 6 month old infant.

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Used in
1.Evaluation of Psychopharmacological agents
2.Teratogenic and Carcinogenic Activity
3.Anti Ulcer & Liver Physiological Studies
4.Assay of Hormones & Acute/ Chronic analgesics
5.Antihypertensive Effects
6.Isolated Preparation- Uterus, Fundus Strip, Colon

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GUINEA PIG

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GUINEA PIG (Cavia porcellus)
• Most useful and docile laboratory animal
• Newborn GP can eat solid food by 5th day
• Young GP best mated after 3 months – polygamous
mating
• Maturation is slow in males than in females
• Not able to synthesize the required vitamin C daily

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• Highly sensitive to histamine & penicillin
• Very susceptible to mycobacterial infection and
anaphylactic shock
• Uterus - inhibited by adrenaline
• Serum contains asparginase – anti-leukemic action
• In this species, dopamine causes fall in BP

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Used in
1.Evaluation of bronchodilator (Anti-Asthmatic)
2.Sensitization Studies - Egg Albumin and Horse
Serum.
3.Study of local anesthetics
4.Bioassay of Digitalis, Histamines, and acetyl choline
5.Study of Vitamin C metabolism & anti-TB drugs

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6.Sensitive cochlea – suitable for hearing experiments
7.More resistant to hypoxia – suitable for oxygen
consumption experiments
8.Isolated preparation of Ileum - Screening of
spasmodic and anti-spasmodic compounds
9.Other isolations – tracheal chain, vas deferens etc.

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GERBIL

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GERBIL (Meriones unguiculatus)
• Mongolian gerbil – small laboratory animal ; length
in between rat and mice – “ Sand rat”
• Originally developed in japan as lab animals
• Ease in handling, mild and quiet in nature
• Used in the field of stroke, epilepsy, auditory
studies, parasitic & bacterial infections and lipid
metabolism & heart disease studies

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HAMSTER
Syrian hamster
Chinese hamster
European hamster

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HAMSTER (Mesocricetus auratus)
• 3rd most commonly used animal in biomedical
research
• Strains :
Syrian hamster (Golden)
Chinese hamster (striped back)
European hamster & Armenian hamster (Gray)

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• Syrian hamsters : free from spontaneous disease and
susceptible to many pathogens
Used in virology, cancer, genetics, toxicology and
reproductive physiology studies
• European hamsters : larger than other hamsters
Suitable – highly concentrated and prolonged
smoke inhalation studies

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• Armenian hamsters : more specific for mutagenic
and carcinogenic studies
• Chinese hamsters :
• Has lowest no. of chromosomes compared to other
lab animals; Useful for cytogenetic studies
Defective β cells in pancreas – used in diabetic
studies

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Advantages
1.Availability and Ease in reproduction
2.Anatomical and physiological features with unique
potential for study
3.Rapid development with short life cycles
4.Cheek pouch : lack of lymphatic drainage ; ideal
site for tissue transplants such as tumors and grafts
5.Pouch isolation - Assay of Prostaglandin E& F

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RABBIT

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RABBIT (Oryctolagus cuniculus)
• Very docile
• Newzealand white rabbit – most common strain
• Homologous to humans to react similarly to diseases
and medications
• Cannot vomit and sensitive to histamine like rodents
• Has an ability to taste water - absent in rodents

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• Dopamine causes fall in BP
• Presence of atropinesterase – degrades atropine
• Doesn’t have adrenergic vasodilator nerves – no
vasomotor reversal phenomenon
• Has huge caecum and long appendix
• Ear veins – convenience for injection & blood
withdrawal

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• Only known mammal from which tubules of the
kidney can be dissected with basement membrane
intact
• Absence of CYP3A4
• Lack of melanin – ‘Albinism’
• Uterus – stimulated by adrenaline

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Used in
• Pyrogen Testing
• Anti Diabetic Study & Topical agents study
• Bioassay of Insulin, curare and sex hormones
• Capillary Permeability Study
• Embryo Toxic and Reproductive studies
• Isolated preparation : heart, duodenum, ileum

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MONKEY

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MONKEY (Macaca mulatta)
• Rhesus species – commonly used
• Structure and function – closely resemble to man
• Uterus resembles human & exhibiting regular
menstrual periods
• Metabolic pattern & Brain structure – same as man
• Require regular check up & timely immunization

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Used in
1.Infertility studies
2.Virology, Parasitology & Immunological studies
3.Immunosuppressant & Nutrition related studies
4.Ideal model for pharmacokinetic studies
5.Best for studying drugs acting on CNS, CVS and
GIT

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SQUIRREL MONKEY
• Most commonly used neotropical primates in US
• Plasmodium species are host specific - important
animal model for malaria vaccine development
studies
• One of the most susceptible non - human primate
species to experimental infection with Creutzfeldt -
Jakob disease & spongiform encephalopathies

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DOG

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DOG (Canis familiaris)
• Most preferred large experimental animal
• Can be easily trained for behavioral activity
• Stomach and intestinal tract resembles human
• Distinct structure of pancreas
• May develop spontaneous Diabetes &Hypertension

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• Cervical sympathetic and vagal nerves run together
inseparable – vagal stimulation causes reflex
variations in blood pressure
• Animal of choice for studies on gastric secretion and
digestion
• Preferred for Anti hypertensive, cardiovascular,
Diabetes and anti ulcer experiments.

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CAT

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CAT (Felis catus)
• Similar physiological features with humans
• Ease of collecting blood samples – useful in studying
the transmission of vitamins & minerals to the fetus
• Thick nictiating membrane – used in screening of
ganglionic blocking drugs
• Able to produce methemoglobinemia – suitable for
toxicity studies

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• Cats are used for the studies where stable BP is
required
• Morphine produces excitation in CNS
• Adrenaline – stimulates the pregnant uterus &
inhibits the null uterus
• Essential in the study of the nerve centres in the
brain

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PIG

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PIG (Sus scrofa domestica)
• Similar in Human physiology
• Less hairy skin – preferred for skin related studies
• Small lungs – susceptible to bronchitis & pneumonia
• Alimentary tract resembles human – used in
digestive system studies
• Important model – Cardiovascular research such as
MI, atherosclerosis etc.

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ZEBRA FISH

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ZEBRA FISH (Danio rerio)
• Dr.George streisinger – Father of zebra fish research
• Optically translucent embryos
• Clear eggs – developed outside the mother’s body ;
allows watching a egg grow into a newly formed
fish in 2-4 days
• Length is 5-6 cm ; Life span is approx. 5 years

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Advantages :
1.Cheaper to maintain than other animals
2.Suitable model for vertebrate development and
genetic studies
Drawback : Not closely related to humans
Glofish : Genetically modified florescent fish
- Tool for examining the erythrocyte development
& circulation defects in embryo

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FROG

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FROG (Rana tigrina)
• Only tailless experimental amphibian
• Frog and toad – differentiated by their appearance
only ; Heart contain 3 chambers
• Vagal response – varies by species & seasonal
• Adrenaline – neurotransmitter in sympathetic system
• Important substances – obtained from various species

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Used in
• Used for determining the retinal toxicity of drugs
• Used in study of the action of drugs on the CNS,
CVS, Neuromuscular junction and pregnancy assays
• Cloning and embryological researches

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CHICKEN

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CHICKEN (Gallus domesticus)
• Widely used due to easy availability and
maintenance
• Only model – studying avian diseases
• Studies related to breeding, genetics, performance
testing, embryology, fertility, toxicology etc.
• Important models – chick comb method,
scleroderma models, autoimmune thyroiditis etc.

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PIGEON

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PIGEON (Columbia livia)
• Mainly preferred for screening of anti emetic
activity
• Spontaneous arteriosclerosis – cardiovascular
studies
• Apomorphine induces stereotypic behavior
• Standardization of cardiac glycosides
• Screening of intravenous anesthetics
• Pigeon crop method – prolactin bioassay

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SUMMARY
• Animal selection – based on how it is closer to
human
• Mice & Rats – commonest experimental model for
various studies
• Guinea pig – very docile; requires vitamin C daily
• Gerbil – auditory studies
• Rabbit – able to taste water; pyrogen testing

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• Hamster – presence of cheek pouch – site for tissue
transplant & graft studies
• Monkey – very closer to human ; metabolic studies
• Dog – GI drug studies; nerve conduction studies
• Pig – skin related studies
• Frog – pregnancy assays; chemicals isolation
• Pigeon – screening model for anti emetics

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REFERENCES
• Medhi B, Prakash A. Practical manual of
experimental and clinical pharmacology. Jaypee
Brothers Medical Publishers; 2010.
• Ghosh M. Fundamentals of experimental
pharmacology. Indian Journal of Pharmacology.
2007 Jul 1;39(4):216.
• Gupta.SK. Drug screening methods. 3rd edition.
New Delhi: Jaypee brothers; 2016

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