Commonly Used Experimental Animals In Pharmacology Laboratory

Laboratory animals are those animals which can be bred and maintained in the laboratory under suitable conditions by the taking permission of regulatory authorities. Guinea pig has become synonymous to the experimental animals, but many other species are equally useful in the study of drugs. Preclinical studies of experimental pharmacology involve laboratory animals using wide‐ranging doses of the study drug to obtain preliminary efficacy, toxicity and pharmacokinetic information. Such tests assist pharmaceutical companies to decide whether a drug candidate has scientific merit for further development as an investigational new drug. Preclinical study involves the use of laboratory animals. Experimental animals can be classified as:

1.     Rodents- Rat, Mouse, Guinea pig, Hamster etc.

2.     Non rodents- Rabbit, Dog, Cat, Pig, Monkey etc.

3.     Miscellaneous- Frog, Pigeon, chicken etc.

The commonly used laboratory animals in pharmacology laboratory are Frog, Rat, Mice, Guinea pig, Hamster and Rabbit. Cats and dogs are used to study the blood pressure experiments. Monkey, pig and some other animals were also used earlier. But now their use has been restricted. However, Beagle dogs are the only strain approved by USFDA for testing of new drugs.

RAT (Rattus norvegius): 

RAT

Rat is a warm blooded rodent which is the most commonly used animal for biomedical research. Rat does not vomit due to lack of vomiting center and tightly presence of lower esophageal sphincter. It has no tonsils and gall bladder in its body. It has diffuse pancreases, thus difficult to perform pancreatectomy to induce type 1 diabetes mellitus. Fundus and pyloric parts of stomach have clear lining between them and gastric acid secretion is continuous. Rat is a coprophagy animal that eats their own stool. It shows resistance to the effect of Cardiac glycosides. Oestrus cycle appeared at puberty at the age of two to three months and cycle lasts for about four to five days. The cycle can be divided into four stages as follows:
Estrus: It lasts for 9-15 h. The vaginal smear shows cornified epithelial cells. It is characterized by sexual receptivity when the female will allow copulation. It ends with ovulation. It can be induced experimentally by administration of diethylstilbestrol (100 mg/kg).

      Met-estrus: Its about 20 h and occurs shortly after ovulation. The vaginal smear consists of many leucocytes with few cornified epithelial cells.

         Di-estrus: It is the longest phase of about 60-70 h. The vaginal smear shows leucocytes only.

       Proestrus: It lasts for about 12 h. The vaginal smear shows nucleated epithelial cells either singe or in groups.

Wistar rats and Albino Sprague-Dawley rats have been widely used strains throughout the world. Lewis and porton strains are also used for experimental purposes.

MOUSE (Mus musculus):

MOUSE

Mice are worm blooded rodent which are the smallest laboratory animals. In biomedical research mice are preferred over other species because they can be bred uniformly, cheap and easy to handle, require small place for housing and very sensitive to small doses of a drug substances. Due to the large similarity in mice and human genome, it provides good model for research on wide variety of human diseases. Swiss albino mouse is the most widely used strain for pharmacological experiments. Laca and Balb-C strains are also used for experimental purposes.

GUINEA PIG (Cavia porcellus):

GUINEA PIG

Guinea pigs name itself has become synonymous to an experimental animal. Guinea pig is a warm blooded rodent and very docile laboratory animal. It is an herbivorous animal and daily requires vitamin C in diet like human. Guinea pig is highly sensitive to histamine. They are very susceptible to tuberculosis and anaphylactic shock. Penicillin is more toxic to Guinea pig than to the mouse. Guinea pig serum contains an enzyme asparaginase, which has antileukemic action.

HAMSTER (Mesocricetus auratus):

HAMSTER

Hamsters are a brown to gold colour animal, have chunky body with short legs, a diminutive fluffy tail and a large amount of loose skin covered with dense short soft fur. There are four toes on the front foot and five on the back. They have prominent cheek pouches extending up to the shoulder region. The ears are quite prominent, rounded, usually pigmented and scarcely covered with hair. The most common strain used in pharmacological studies is the Syrian or Golden hamster, Chinese hamster, European hamster and American hamster.

RABBIT (Oryctolagus cuniculus):

RABBIT

Rabbit is a worm blooded mammalian and a docile animal used for various studies. Some strains of rabbit are resistant to the effect of atropine because they have higher concentrations of Atropinesterase enzymes in their blood. In rabbits coitus itself induces secretion of leutenising hormone (LH) in females, which leads to ovulation. Progesterone is known to block such ovulation. New Zealand white rabbits are the most common strain used widely in pharmacological studies. Other strains which are also used in studies are the Dutch, the Flemish Giant, Himalayan black and some of the domestic strains.

FROG (Rana tigrina):

FROG

Frog is a cold blooded amphibian which is used very commonly in the biomedical research. Frogs and toads have no taxonomic differences but can be differentiated by their appearances (frog is wet and toad is dry). It has three chambers in its heart, two auricles and one ventricle. The oxygen and moisture are absorbed through their highly permeable skin. Some hybridized frogs are used in biomedical research are Rana esculenta, Rana pipiens, Rana temporaria, Rana lessonae, Rana ridibunda etc.

Table 1: Uses of different laboratory animals in experimental pharmacology.

ANIMALS	USES IN EXPERIMENTAL PHARMACOLOGY
Frog	a)     Commonly used for bio-assays and in pregnancy assays. b)    Different drugs acting on central nervous system, neuro-muscular junction and heart can be studied using frog and its isolated tissues. c)     Whole frog is also used in screening of central drugs like local anesthetics.
Rat	a)     The rat and its isolated tissues are used in the screening of drugs acting on central nervous system, cardiovascular system, estrus cycle, mating behavior, gastric ulcers and acid secretions in stomach. b)    Rats can be trained properly for various types of work performances in response to a reward or punishment, hence suitable for testing of psycho-pharmacological agents. c)  It is also useful in the hormonal assay, immunity, transplantation, immuno-suppression, carcinogenicity study and different toxicity studies. d)   The isolated tissues like ileum, trachea, heart, anacoccygius muscle, stomach strip, vas deferens, uterus and phrenic nerve-diaphragm are used in experimental pharmacology.
Mouse	a)     Mice are the widely used animal in different toxicity studies. b)    Mice are also used in cancer and genetics research, immunity, transplantation related experiments. c)     Screening of analgesics, central nervous system and chemotherapeutics are carried out in this species. d)    Isolated tissues of mice are rarely used (except vas deferens and ileum) in the experimental pharmacology because they are very small and delicate. e)     They were earlier used in the bioassay of insulin.
Guinea pig	a)     It is mainly used in the bio-assay of Histamine. b)    They are used in the study of drugs like broncho-dilators, local anesthetics, spasmolytic and digitalis. c)     The drugs affecting the hearing activity are also screened using Guinea pigs. d)    They are widely used in immunology. e)     The drugs inducing anaphylaxis and hypersensitivity are screened using Guinea pigs. f)     It is also useful in screening of drugs for the treatment of tuberculosis, cholera and amoebiasis. g)    The isolated tissues like ileum, tracheal chain, vas deference and heart are used in experimental pharmacology.
Hamster	a)     The presence of cheek pouch in hamster makes it useful in immunological research. b)    Syrian hamsters are used in the research field of virology, cancer, genetic, toxicology and reproduction. c)     Chinese hamsters are commonly used in diabetes due to deficiency of beta cells, or presence of defective beta cells in the pancreas. d)    Chinese hamsters have a low chromosome number (22) compared to other laboratory animals due to which they are used for cytological investigations, genetics and tissue culture. e)     Hamsters are also used in Onco virus, influenza virus, respiratory syncytial virus studies and vaccine production. f)     Cheek pouch doesn’t have lymphatic drainage and hence they can be used as a site for tissue transplant such as tumors and grafts. g)    The stomach pouch strips of Syrian hamster have been used for the essay of prostaglandins.
Rabbit	a)     Rabbits are mainly used in the pyrogen testing, in bioassays of insulin and sex hormones. b)    They have been used in the screening of drugs for diabetes, diphtheria, tuberculosis, cancer and heart diseases. c)     They are commonly used in genetics, nutrition, toxicology, immunology, physiology and reproduction. d)    They are also useful in the study of teratogenicity of the drugs. e)     Isolated tissues like duodenum, ileum and heart are used in experimental pharmacology. f)     Bi-oassay of Adrenaline can be performed using rabbit ileum. g)    It is an ideal animal for pharmacokinetic studies. h)    Apart from the drugs, effects of creams, cosmetics, special diets and food additives have also been tested in rabbits.
Dog	a)     The dog is used as a model for cardio vascular research, diabetes mellitus, ulcerative colitis, open heart surgery, organ transplantation, central nervous system, pharmacology and toxicology studies etc. b)    Anaesthetized dogs are commonly used in the study of drugs acting on blood pressure and vascular system.
Cat	a)     Cat has distinct nictiating membrane (third eyelid), which is commonly used in screening of ganglionic blocking drugs. b)    Cats are mainly used in behavioral studies, cardio vascular studies, nerve impulse transmission etc. c)     It is also used in neuropharmacology, toxicology, oncology and chromosomal abnormalities studies. d)    It is also employed for the study of drugs effecting on blood pressure.
Monkey	a)     The monkey is used in the fields of virology, parasitology, immunology and immunosuppression. b)    It is also employed for the study of nutrition, reproduction etc. c)     Adult rhesus monkeys are used for N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered model of parkinson’s disease.
Pig	a)     They are used in pharmacological and toxicological research. b)    They are used in important research areas like several isolated organ models, investigation of skin permeation and for digestive systems.
Pigeon	a)     They are used in screening of antiemetic activity, cardiovascular diseases, CNS disorders and intravenous anesthetics. b)    Bioassay of prolactin through the pigeon crop method is one of the important methods.
Chicken	a)     They are used in many areas of biomedical research such as breeding and genetics, growth, embryology, incubation, fertility, artificial insemination, toxicology, physiology, biochemistry, endocrinology and neurobiology. b)    Chick comb method, heart rate, EEG, memory, angiogenesis, blood pressure measurement and vasodilating activities like different models can be developed in chicken.

Table 2: Biological and physiological data of commonly used laboratory animals.

Parameter	Rat	Mouse	Guineapig	Hamster	Rabbit
Adult weight (g)	150-300	20-40	600-800	80-150	1000-3500
Life span (years)	2-3	1.5-2.5	3-5	2-3	4-7
Suitable age for experiment (Months)	1.5	0.75	3	1	6
Gestation period (Days)	21-23	19-21	68-72	16	31-32
Daily food intake (g/ 100 g body weight)	5-10	15-20	6-8	7-10	5-7
Daily water intake (ml/100 g body weight)	10	20	10	10	10
Rectal temperature (ºC)	36-46	38-39	37.2-40	37-38	38.5-40
Heart Rates (beats/ min)	300-500	330-780	230-400	300-500	130-300
Systolic blood pressure (mm Hg)	116	113	77	108	110
Diastolic blood pressure (mm Hg)	90	81	47	77	80
Blood volume (ml/ Kg)	6-7	7-9	6-12	6-9	4-8
Respiratory rate (min)	65-180	84-230	70-104	33-127	38-60

BIBLIOGRAPHY

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