Animal Models in Preclinical Research

Animal Models Used To Screen Various Activities

Animals commonly used

 Male Sprague Dawley rats

 Albino Swiss rats
 Male wistar rats
 Female cynomolgus monkeys
 Rabbits
 Hamsters

ANIMAL MODELS FOR SCREENING OF ANALGESIC ACTIVITY

In Vivo methods

 Hot plate method

 Tail flick model
 Cold ethanol tail flick test
 Electric stimulation of tail
 Monkey shock titration test
 Formalin test
 Writhing test
 Rat sigmoid colon test
 Inflammatory uterine pain model
 Haffner’s tail clip method
 Randal selitto test

In Vitro Methods

 H-Naloxone Binding Assay

 Opiate receptor binding assay
 Receptor binding of cannabinoids

Animal Models Used to Screen Anti-Inflammatory Activity

In vivo methods

 Cox assay
 Mast cell degranulation
 Adhesion assays
 Platelet neutrophils adhesion
 Cell based receptor gene assay
 FMLP induced O2 generation by polymorphonuclear cells (PMNS)
 FMLP induced adhesion of PMN by HUVEC

In vitro methods

 UV-B induced erythema in guinea pig

 Carrageenan induced paw edema model
 Plural pellet induced granuloma
 Adjuvant arthritis
 Air pouch model

Animal Models Used To Screen Muscle Relaxant Activity

In vivo models

 Rota rod test in mice

 Chimney test in mice
 Grip strength in mice
 Inclined plane test in mice

Animal Models Used To Screen Anti Convulsant Activity

In vivo methods

 Threshold models
 Maximal electro shock seizure test
 Psychomotor seizures test
 Focal electrical stimulation such as kindling

In vitro methods

 Hippocampal slices model

 Electric recording from isolated brain cells
 GABA receptor binding assays
 Excitatory amino acid receptor binding assays

Animal Models Used To Screen Anti depressants Activity

In vivo methods

 Water wheel model

 Learned helplessness test
 Tail suspension test
 Reserpine induced hypothermia
 Amphetamine potentiation
 Resident intruder paradigm
 Muricidal behaviour in rats

In vitro methods

 Inhibition of 3[H]-norepinephrine uptake in rat brain synaptosomes

 Inhibition of 3[H]-dopamine uptake in rat striatal synaptosomes

 Binding to monoamine transporters

 Radioligand binding assays

Animal Models Used To Screen Anxiolytics Activity

In vivo methods

 Elevated plus maze

 Light dark model [two compartment box ]
 Social interaction
 Isolation induced aggression
 Vogel’s lick conflict model
 Marble burying test

In vitro methods

 GABA - A receptor binding

 GABA -B receptor binding
 Benzodiazepine receptor 3 [H] flunitrazepam binding assay
 Serotonin [5 H] receptor binding of 3[H] -8 – hydroxy 2- di n – propyl amino tetralin [H]
DPAT

Animal Models Used To Screen Antihyperlipidemic Activity

In vitro methods

 Inhibition of isolated HMG CoA reductase inhibitors

 ACAT inhibitory model

In vivo models

 Tritan wistar rat induced hyperlipidemia

 Cholesterol diet induced atherosclerosis in rabbits
 Hereditary hyperlipidemia in rabbits
 Transgenic animal model

 Hypolipidemic activity in Syrian hamsters

Animal Models Used To Screen Anti diabetic Activity

In vivo models

 Chemically induced diabetes

 Insulin antibody induced diabetes
 Hormones induced diabetes
 Virus induced diabetic animal model
 Spontaneously/genetically derived animals
 Zebrafish model

In vitro models
 Isolated pancreatic islet cell lines of rats

 Invitro studies on glucose uptake

a) Cultured human primary myotubes

b) Marine 3T3-L1 cells

 Mouse pancreatic islet isolation and intracellular CAMP determination

 GLUC-HET chick embryo models

Animal Models Used To Screen Hepatoprotectives Activity

In vivo methods

 Hepatitis in long Evans cinnamon rats

 Temporary hepatic ischemia
 Induced liver fibrosis in rats by carbon tetrachloride
 Bile duct ligation induced liver fibrosis in rats
 Thioacetamide induced necrosis of liver
 Paracetamol induced liver damage in rats
 Rifampicin + isoniazid induced hepatotoxicity in rats

In vitro methods

 Primary hepatocyte cell culture

 Stellate cell culture
 Kupffer cell culture
 Liver cirrhosis and necrosis
 Inhibition of proline hydroxylation

Animal Models Used To Screen Anti Cancer Activity

In vivo methods

 Carcinogen induced models

 Viral infection models
 Transplantation models
 Genetically engineered mouse models
 In vivo hallow fibre assay

In vitro methods

 Tetrazolium salt assay

 3H-thymidine uptake
 Dye exclusion test
 Clonogenic test
 Cell counting assay
 Morphological assay

References :

1. Parmer, Vogels, Rang and Dales Textbooks.

2. Hans GV. Drug Discovery and Evaluation: Pharmacological assays. Springer 3rd
edition. New York: Springer -Verlag Berlin Heidelberg ;2008.
3. Gupta SK. Drug screening methods (Pre clinical Evaluation of New Drugs). 2nd
edition. New Delhi: Jaypee Brothers Medical Publishers; 2009.
4. Wolfgang L. Critical review of current animal models of seizures and epilepsy used
in the discovery and development of new antiepileptic drugs. Seizure.2011(20):359-
368.

P. JITHENDRA PRASAD

19P91R0080 .