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Biology and medicine of the rat

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In: Laboratory Animal Medicine and Management, Reuter J.D. and Suckow M.A. (Eds.).
International Veterinary Information Service, Ithaca NY (www.ivis.org), Last updated: 29-Sep-2004;
B2503.0904

Biology and Medicine of Rats

K. R. Pritchett 1 and B. F. Corning 2
1,2 Charles River Laboratories, Inc., Wilmington, MA, USA.
1 Department of Comparative Medicine, University of Washington, Seattle, WA, USA.

Table of Contents
I. Introduction
A. History and Use in Research
B. Behavior
II. Biology
A. Anatomy
B. Reproductive Anatomy and Physiology
III. Husbandry and Management
A. Handling
B. Housing and Feeding
C. Blood Sampling and Substance Administration
D. Euthanasia
IV. Surgery and Anesthesia
A. Anesthesia and Analgesia
B. Surgery
C. Castration
D. Ovariohysterectomy
E. Removal of Mammary Neoplasms
V. Diseases and Medicine
A. Infectious diseases
1. Respiratory Disease
2. Sialodacryoadenitis Virus (SDAV)
3. Diarrhea
4. Tyzzer's Disease
5. Ectoparasites
6. Endoparasites
B. Noninfectious diseases
1. Barbering
2. Dermatitis
3. Conjunctivitis
4. Malocclusion
5. Mammary Fibroadenoma
6. Megaloglobus
7. Myocardial Disease
8. Nutritional Deficiencies
9. Renal Disease
10. Retinal Degeneration
11. Ringtail
12. Urinary Calculi
C. Zoonotic diseases
1. Allergic Disease
 2. Hantaan Virus
3. Leptospirosis
4. Ornithonyssus bacoti
5. Rat Bite Fever
6. Ringworm
7. Rodentolepis (Hymenolepis) nana
8. Salmonellosis
VI. Acknowledgements
VII. Recommended Reading for the Practitioner and References

I. Introduction
A. History and Use in Research
"Rat" refers to a wide variety of small animals of the family Rodentia. They tend to have coarse fur in dull colors such as
brown and black, hairless tails, and powerful incisors, with which they can gnaw through hard materials. Most rats seen in
private practice and used in a laboratory setting today are domesticated Norway rats, Rattus norvegicus. This animal’s
original natural habitat was the steppes of Asia, but at some point in the 1600s, conditions changed and the rat became
commensal with man, spreading throughout the world [1].
The path to domestication for Norway rats probably began in France and England in the 1800s, in association with rat
baiting. Rats were captured and held in large numbers for the sport of rat baiting, in which trained terriers were timed to see
how long it took them to kill a certain number of rats in a pit. The albino mutation is relatively common in the general rat
population, and these animals were probably set aside as a curiosity, and later for breeding and show purposes. Some rats
may have found their way from those first rat fanciers into laboratories [2].

In the 1850s, rats made their initial appearance as laboratory animals. Norway rats are widely regarded as the first species
to be domesticated for scientific purposes [2]. In the laboratory, they are used today to study human and animal physiology,
basic neuroscience, genetics, infectious and inherited diseases, and many other scientific disciplines. Rats, like mice, are
tolerant of continued inbreeding. There are many strains of inbred rats commonly available. This genetic homogeneity
allows them to serve as models for many human conditions. Common inbred rat strains include the Brown Norway,
Fischer, Lewis, and F344. Outbred stocks of rats are also available from commercial suppliers. With their genetic
heterogeneity, they are thought to better mimic the diverse genetics of human populations. They are often used in
toxicology and drug development work. Common outbred rats include Wistar, Long-Evans, and Sprague-Dawley. There
are also many specialized strains of rats being bred for laboratory use, including consomic rats, which are rats of one strain
that carry whole chromosomes from another strain and rats with spontaneous genetic mutations, such as athymic nude rats,
and the various obese and diabetic rats. Rats are becoming the most important animal models in the study of diabetes,
obesity, and hypertension. Researchers found manipulating the rat embryo more difficult than the mouse embryo, so rats
have lagged behind in the transgenics race. However, those difficulties have been conquered and transgenic rats are being
created in ever greater numbers.

Today, rat fanciers abound, with hobbyists breeding rats for show and sale. These fancy rats are kept as pets and bred for
many coat colors and varieties of pelage as well as characteristics such as large ears or short tails. There are numerous
"ratteries" in every urban area in the United States, and there are rat fanciers’ associations in North America, Europe,
Japan, and Australia. Despite the prejudice associated with their well-deserved reputation as economic pests and carriers of
disease, domesticated rats can make fine pets. Some of the wild rat species are occasionally kept as pets, but this is not
recommended (e.g., the recent monkeypox outbreak in the United States), and these species will not be addressed.

B. Behavior
Rats are curious, intelligent creatures that exhibit a wide variety of behaviors. They tend to be docile, showing aggression
only in defense of their young. Some strains, however, are more aggressive than others. Rats can be trained to perform
certain behaviors through the use of positive reinforcement. Some common behaviors in rats include standing (rearing up
on their hind limbs), which is used to explore the environment, wrestling, which is a form of play in young rats, and
grooming. Rats are not as neophobic as some rodents and will readily interact with new objects placed in their
environment. Some objects suitable as toys for rats include Nylabones, PVC pipe, running wheels, and manipulanda, such
as marbles or nuts and bolts. As with most rodents, however, rats find the presence of a conspecific more enriching than
any toy. Rats are social animals and should not be housed singly if at all possible. If toys are used in the laboratory setting,
they should be: approved by the Institutional Animal Care and Use Committee, suitable for the research being conducted,
disposable or easily sanitized, and regularly examined for damage that could result in harm to the animals.
Rats may spend a good deal of their time standing. As quadrupeds, rats normally stand and move about on all four feet. In a
bipedal standing posture, the animal may be stretched to its full length, with its hind legs extended, or may squat with its
hind legs contracted beneath it, but its body held erect. The latter posture is the preferred posture for eating, drinking and
grooming. Rats are nocturnal creatures, with their highest activity levels at night, but they are light sleepers, waking often
during the day. A sleeping rat will tuck its head between its paws and its tail around its body. They often sleep huddled
together in a corner of their cage or in a dark area, if one is provided. Rats may also sleep sprawled out on one side. Unlike
mice, rats vary in their use of nesting material, with some strains and individuals making more use of such material than
others. A pregnant or nursing female rat, however, will often take advantage of nesting material to prepare a nest for her
pups.
Rats can hear into the ultrasonic range, and their vocalizations, especially those of young pups or aroused adults, extend
into the ultrasonic range as well. Their hearing range at 70dB is 250 Hz to 70 kHz, with the most sensitive range from 8 -
32kHz. The ultrasonic portion of their communication is very important to the bonding of mother to young. When young
rats are outside of the nest, they may squeak surprisingly loudly. This squeak has a large ultrasonic component, which
alerts adult rats to their whereabouts. Rats will squeak and squeal when aroused or disturbed. They may also purr or
chirrup, both of which usually indicate contentment.
Pheromones are an important part of the rat communication repertoire. These are transmitted through urine, sebaceous
glands, and fecal matter. Using these pheromones, rats recognize kinship, social status, and sexual receptivity. Rats also
respond to alarm pheromones from other rats [3].

II. Biology
A. Anatomy
The average life span of the domestic rat is 2.5 - 3.5 years. Exceptional members have been recorded at 5 years, but this is
uncommon. An adult female rat reaches 250 - 300 g body weight at adulthood (higher during pregnancy) and an adult male
rat reaches 400 - 500 g adult body weight. A distinguishing feature of rodents, including rats, is the absence of canines and
the presence of prominent incisors. Rats are monophydontic, meaning they grow one set of teeth in their lifetime. The
enamel of the rodent incisor contains iron, which gives it its yellow-orange color and its hardness Fig. 1. These incisors
grow continuously and must be worn down through gnawing. The molars are also open-rooted, but they wear on each
other, and are only rarely misaligned. The dental formula of the rat is 2(1/1 0/0 0/0 3/3) = 16 and the vertebral formula is
C7 T13 L6 S4 Cd 27-30.

Figure 1. Normal rat dentition. Note the yellowish incisors and sharp gnawing surface. - To view this
image in full size go to the IVIS website at www.ivis.org . -

Rats are mammals and as such, possess many similarities with other mammals. Only the peculiarities of the rat’s anatomy
are addressed. For clinical pathology and other normative biological data, please see Table 1, Table 2, Table 3, Table 4,
Table 5 and Table 6. A rat’s esophagus is lined entirely with keratinized epithelium. The stomach of the rat contains both a
non-glandular and glandular portion, which are separated by the limiting ridge. The esophagus enters the stomach through a
fold in the limiting ridge and this anatomic feature prevents rats from vomiting. The small intestine of rats is unremarkable,
but rats possess a prominent cecum, which occupies much of their abdominal cavity. The rat has a four-lobed liver with no
gall bladder. The pancreas is diffuse. The inguinal canals remain open throughout life.

Table 1. Normal physiological data for the rat [8,9]. As with all "normal" values, these values and the values
presented in the other tables in this work, may not represent the mean or range for certain populations or
strains of animals. For this reason, the values should be interpreted as approximations.
Life expectancy 2.5 - 3.5 years
Body weight - male 300 - 500 grams
Body weight - female 250 - 350 grams
Body temperature 36.0 - 37.5°C (96.5 - 99.5°F)
Daily food consumption (adult) 5 g/100 g BW
Daily water consumption (adult) 8 - 10 ml/100 g body weight
Daily urine production 5 - 6 ml/6 ml body weight
Urine pH 7.3 - 8.5
Urine specific gravity 1.04 - 1.07
Daily fecal production 10 - 15 grams
 Table 2. Normal respiratory parameters for the rat [8,9].
Respiratory rate 70 - 110 breaths/min
Tidal volume 0.5 - 2.0 ml
Minute ventilation 75 - 130 ml/min
Trachea diameter 1.6 - 7.7 mm
Alveolar surface area (400 gram rat) 7.5 m 3
Total lung capacity 11.3 +/- 1.4 ml
Vital capacity 8.4 +/- 1.7 ml
Functional residual capacity 3.9 +/- 0.8 ml
Residual volume 2.9 +/- 1.0 ml

Table 3. Normal cardiovascular parameters for the rat [8,9].

Heart rate 250 - 500 beats/min
Mean systolic arterial blood pressure 116 mm Hg
Mean diastolic arterial blood pressure 90 mm Hg
Cardiac output 50 ml/min
Blood volume 6 ml/100 gram body weight
Sample volume 2 - 4 ml
Sample site Lateral tail vein; saphenous vein
pO 2 93.2 mm Hg
pCO 2 39.9 mm Hg
Arterial blood pH 7.41
H+ 38.6 +/- 0.6 nM
Base excess +1.8 +/- 0.4

The rat’s lungs are immature at birth and lack alveoli, alveolar ducts, and respiratory bronchioles. Remodeling occurs 4 - 7
days after birth and respiratory bronchioles are found 10 days after birth. The right lung of the rat has four lobes, while the
left has one. The rat’s pulmonary veins contain cardiac muscle fibers.

Rats have several unique glandular structures. Steno’s gland (lateral nasal gland) is located in the maxillary sinus and it
both humidifies air and controls mucus viscosity. Paired Zymbal’s glands (sebaceous glands) are found at the base of each
ear. They are auditory sebaceous glands that open into the external ear canal. Rats also have Harderian glands (lacrimal
glands), which secrete porphyrin, behind each eye. Secretions from these glands usually go unnoticed unless the rat is ill or
stressed. Then, reddish-brown secretions may be seen rimming the eye or at the external nares. Front paws may also show
staining as the animal grooms the irritating secretions away. These secretions resemble blood, but porphyrin fluoresces
under ultraviolet light while blood does not.
 Table 4. Normal serum biochemistry values for the rat [21]. For a more exhaustive list, including hormones,
the reader is referred to Kohn and Clifford [9].
Glucose (mg/dl) 85 - 132
Urea nitrogen (mg/dl) 32 - 54
Cholesterol (mg/dl) 46 - 92
Total protein (g/dl) 6.3 - 8.6
Albumin (g/dl) 3.3 - 4.9
Globulin (g/dl) 2.4 - 3.9
Aspartate aminotransferase (U/L) 39 - 92
Alanine aminotransferase (U/L) 17 - 50
Alkaline phosphatase (U/L) 39 - 216
Sodium (mEq/L) 141 - 150
Potassium (mEq/L) 5.2 - 7.8
Chloride (mEq/L) 99 - 114
Phosphorus (mg/dl) 6.2 - 11.7
Calcium (mg/dl) 10.7 - 13.7
Magnesium (mg/dl) 2.6 - 3.11

Table 5. Normal hematology values for the rat [21].

Red blood cells (x 10 ul) 5.4 - 8.5
Hemoglobin (g/dl) 11.5 - 16.0
Hematocrit (%) 37 - 49
Platelets (x 10 ul) 450 - 885
White blood cells (x 10 ul) 4.0 - 10.2
Neutrophils (x 10 ul) 1.3 - 3.6
Lymphocytes (x 10 ul) 5.6 - 8.3
Total blood volume (ml/kg) 50 - 65

Like other rodents, rats do not have many physiologic mechanisms to allow them to cope with heat. They cannot sweat and
they cannot pant. Some heat is dissipated through vasodilation in the tail. Although increased salivation is seen as a
response to overheating, rats will not drink more water in response to increased temperature. They will take saliva and
spread it on their heads and bodies in attempts to cool themselves. Rats also thermoregulate through behavioral means such
as burrowing and seeking shade.

B. Reproductive Anatomy and Physiology

A summary of rat reproductive norms may be found in Table 6. Male rats reach puberty at 40 - 60 days of age. Descent of
the testes usually occurs between days 30 - 60. Sperm counts vary by strain [4]. The male rat has an os penis. Male rats
have the following accessory sexual organs: ampulla, seminal vesicles, prostate, bulbourethral glands, coagulating glands,
and preputial glands. The coagulating gland and prostatic and vesicular secretions are responsible for the copulation plug, a
firm plug deposited in the vagina of the female after copulation. (This plug, when found outside the female rat, is capsule-
shaped and approximately 5 mm long.) The male rat has no nipples. The adult male rat has a prominent scrotum and a
longer anogenital distance than the female rat.
 Table 6. Normal reproductive parameters for the rat [8].
Sexual maturity 50 +/- 10 days
Gestation 21 - 23 days
Litter size 8 - 14
Birth weight 5 - 6 grams
Eyes open 10 - 12 days
Ears open 12 - 14 days
Weaning 21 days
Chromosome number (diploid) 42

Young female rats are born with a vaginal closure membrane, called the vaginal plate. This spontaneously ruptures before
puberty (usually at 33 - 42 days of age), but may persist, resulting in a vagina and uterus distended with mucus and other
secretions. Female rats reach puberty at 40 - 60 days of age (approximately 6 - 8 weeks). The female rat is a polyestrus
spontaneous ovulator who cycles every 4 - 5 days. The rat is in proestrus for approximately 12 hours, estrus for
approximately 12 hours, metestrus for approximately 21 hours, and diestrus for the longest portion of the cycle,
approximately 55 hours. Rat estrus cycles can be evaluated through the use of vaginal smears. Vaginal cytology is similar
to that of other animals in that a vaginal smear containing mainly cornified epithelial cells is a good indication of estrus.
Ovulation usually occurs in the middle of the dark portion of the light/dark cycle. Rats are sensitive to changes in the light
cycle, with continuous light readily producing persistent estrus due to polycystic ovaries [5].

The gestation period of the rat is 21 - 23 days and there is a fertile postpartum estrus. The female rat has 6 pairs of
mammary glands and gives birth to an average of 10 - 12 pups. Cannibalism is uncommon, but does occur. It is a natural
way for a dam to rid the nest of weak or ill pups, or may be precipitated by stress, especially in a first-time mother. Rat
pups weigh 5 - 6 grams at birth, and are born blind, deaf, and hairless. Their ears open at approximately 12 days and their
eyes between days 10 - 12. Rat pups are dependent on the female for their nutritional needs until they are approximately 14
days old. Once they are mobile, they may explore food if it is present in the bottom of their cage, but will still receive most
of their calories from milk. During the early food exploration period, young rats may be observed engaged in coprophagy.
This is a normal means of obtaining gut flora and exploring their environment. Most rats are weaned at 21 days of age.
Weaning is usually performed by removing the animals from the home cage and separating the animals into single-sex
groups. Animals from multiple litters may be mixed together at weaning. Animals may be housed at higher densities when
smaller and separated as they become larger.

Rats may be housed in single-sex groups, in monogamous breeding situations, or in polygamous breeding situations. Male
rats tolerate the company of other males quite well and may be housed together in single-sex groups. If breeding rats, the
monogamous configuration allows for absolute knowledge of both maternity and paternity. Housing a male with more than
one female allows for sure knowledge of paternity, but maternity may be confusing. Female rats will gang-nurse litters, and
male rats will participate in care of the young. Housing more than one male with a group of females will result in fighting
between the males.

III. Husbandry and Management

A. Handling
Although generally docile creatures, rats may object strenuously to being handled inappropriately. If attempting any
restraint procedure for the first time, it is best to practice on a very young rat or a rat-sized stuffed animal. Larger or heavier
rats do not enjoy being handled by their scruff or dorsal skin and will usually object with loud squeals and attempts to bite
or escape. Young, docile rats may be handled by the scruff for minor procedures (Fig. 2). The best way to remove a rat
from a cage for an exam is to gently grasp it close to the base of the tail and lift it from the cage. The rat should not be
dangled by the tail or lifted by the tip of the tail, as tail slip (degloving of the skin), necessitating tail amputation, may
occur. After lifting, the rat should be brought to the other forearm and placed there, with a hand remaining on the rat’s tail.
This is an acceptable way to carry a rat for short distances (Fig. 3).

Figure 2. Scruffing a rat for restraint purposes. - To view this image in full size go to the IVIS website
at www.ivis.org . -
 Figure 3. Acceptable placement for carrying a rat for short distances. Notice how the handler has the
rat firmly by the base of the tail. - To view this image in full size go to the IVIS website at
www.ivis.org . -

Alternatively, the rat can be placed on a solid surface, such as a tabletop, for further manipulations. For minor
manipulations, the rat may be restrained by hand. The rat is placed on a flat surface and the tail is grasped in one hand. The
other hand is positioned over the rat’s shoulder blades. The restraining hand reaches down and using the thumb and
forefingers, firmly grasps the rat around the thorax, behind (or underneath) the rat’s axillary area. This results in a rat with
its arms lifted and pushed gently so they are lifted or crossed in front (Fig. 4). Care must be taken to not limit the rat’s
breathing by restraining the rat too tightly. The restrainer’s other hand is free to perform a procedure or gently restrain the
hind feet and tail. This posture will keep the rat’s teeth safely away from the restrainer and/or the person performing the
procedure.

Figure 4. Restraint of a rat by grasping it around the thorax. - To view this image in full size go to the
IVIS website at www.ivis.org . -

For more painful procedures, full-body restraint of the rat is recommended. A surgical towel makes an excellent rat
restraint device. Many fractious rats become much calmer when shielded from the bright lights of an exam area by a dark
towel. The rat can be wrapped in the towel, much like a cat may be wrapped in a towel, and relevant parts exposed for
examination or manipulation. Alternatively, the rat can be shepherded into a small plastic bag with a corner cut off to allow
the rat to breathe. (These bags are also commercially available.) The corner should be large enough to allow the rat to poke
his muzzle out, but not his whole head. The rat is encouraged to enter the bag. This method of restraint is stressful to the rat
and may cause overheating. It should only be used for short periods of time for procedures like intraperitoneal injection. If
a practice or laboratory sees a large number of rats, the purchase of a commercial rat restraint may be valuable. It is a clear
plastic cylinder; some have a flattened side (for easier use) with adjustable closing pieces that fit over the tail (Fig. 5). The
advantages of these restraints are that the rats are much more comfortable than in a plastic bag, they may be held longer in
the restraint without fear of overheating, and they provide easy access to the tail and paws. The disadvantages are that they
are more expensive than surgical towels or plastic bags, they must be sized exactly to the rat (and some rats are much too
large to ever fit a commercial restraint), and they often do not allow good access to the abdomen or limbs.

Figure 5. Commercially available rat restraint. - To view this image in full size go to the IVIS website
at www.ivis.org . -

B. Housing and Feeding

Rats may be housed in a variety of cages and on a variety of surfaces. Solid-bottomed and wire-bottomed cages are the
most common, with wire usually used in situations where there are large numbers of animals housed together, or where it is
important that the rat not have access to its own fecal matter. Wire-bottom cages are unsuitable for breeding, as the wire
may injure the young pups. Foot lesions, while still uncommon, are more common in rats housed on wire-bottomed cages.
Foot lesions are more likely in older, heavier animals that have been housed on wire for over a year [6]. Many institutions
are now providing resting areas for animals that must be kept in wire-bottomed cages. The animals will not soil their
sleeping areas if given the chance, and the addition of a small platform or solid area allows the animals to rest off the wire,
further reducing the chance of foot lesions. Animals housed in a wire-bottomed cage may need the litter beneath their cage
changed less frequently than animals housed in solid-bottomed cages. Since the animals are not directly exposed to the
litter, any litter is acceptable, as long as it allows for absorption of urine.

Most solid bottom cages are made from plastics, specifically polycarbonate or polypropylene. If animals are housed in a
solid-bottomed cage, the choice of bedding becomes more important, as animals will eat, sleep, and play in this material.
Cedar or other aromatic woods will induce hepatic enzymes and may cause irritation to mucous membranes. Chipped
hardwood or heat-treated pine bedding is acceptable, as is any commercially available paper product bedding, such as
Alpha-Dri tm or CareFresh tm . Nude rats may develop conjunctivitis from the dust from some paper product beddings. This
should be monitored carefully, or nude rats should be kept on shavings. Newspaper is not a good choice, but unprinted
newsprint will do, although it is not ideal. Litter should be changed when it appears soiled. This may be as infrequently as
once weekly or as frequently as every day, depending on the housing density. Ideally, cages should be sanitized at least
once weekly. Different countries may have different recommendations for housing densities or cage size. In the United
States, The Guide for the Care and Use of Laboratory Animals outlines acceptable housing densities for rats of various
sizes. That information is presented in Table 7.

Table 7. Recommended minimum cage sizes for rats [19].

Weight of rat Floor area (cm 2 ) Height (cm)
Less than 100 g 110 18
Up to 200 g 148 18
Up to 300 g 187 18
Up to 400 g 258 18
Up to 500 g 387 18
Greater than 500 g ≥452 18

Fresh, clean water should be available at all times to rats. Water is best provided using a glass or plastic bottle equipped
with a sipper tube, or through an automatic watering system. Dishes of open water will be quickly dirtied or overturned.
Rats should be fed a hard, pelleted diet designed for use in rodent species. With their constantly growing incisors, a pelleted
feed provides a hard gnawing surface that prevents incisor overgrowth. Rat blocks are available in many formulations and
some companies will incorporate a desired substance, such as hormones or antibiotics, into the feed. The nutrient
requirements of rats are available in print [7-9]. Rats fed ad libitum tend to become extremely fat, especially when kept for
long periods of time. Once the rat has reached adulthood, limiting the amount of food available decreases weight gain and
encourages longevity [10]. Treats should be limited for pet rats. Depending on the health status of the facility and the
experimental status of the animal, treats may be a part of the laboratory rat’s diet. Laboratory-appropriate treats are
available from feed companies. The use of home-formulated treats is not recommended in a laboratory setting.

In the animal facility, 10 - 15 air changes per hour are necessary to dissipate the heat load and environmental CO 2 and NH 3
production of animals. Rats acclimate well to a light cycle of 12 hours of light and 12 of darkness. If better breeding
performance is desired, moving to 14 hours of light a day may increase fertility, as rats are long-day breeders. Albino rats
may show retinal degeneration with exposure to bright lights, so this should be minimized. Temperature and humidity
should be controlled for the comfort and safety of the rats. As mentioned earlier, rats do not thermoregulate well and are
prone to hyperthermia. Recommended temperatures are 21 - 24°C and humidity should be kept between 30 - 70% if
possible. Nude or hairless rats may be kept at a slightly warmer temperature.

C. Blood Sampling and Substance Administration

The most common means of administration of substances in the rat are intraperitoneally, intravenously, and per os, through
oral gavage or administration in feed or water. The lateral tail veins in the rat are large enough to allow for both
administration of drugs or compounds and withdrawal of blood. Blood may also be obtained from the jugular veins, the
lateral saphenous veins, and the orbital plexus. The use of the orbital plexus for blood sampling should only be conducted
on anesthetized animals. As a rough guide, no more than 1% of the animal’s body weight should be taken during a single
blood collection. For example, in a 300 g rat, the total blood volume is approximately 6% of its body weight, or 18 ml One
percent of the body weight is 3 ml Intraperitoneal (IP) injections should be made into the lower left quadrant of the
abdomen (Fig. 6). Maximum injection volume for the IP route is approximately 10 ml Intramuscular (IM) injections should
be made into the quadriceps muscle. As this muscle is quite small, the maximum injection volume should be 0.2 ml,
Intravenous (IV) injections may be performed in the lateral veins of the tail (Fig. 7), IV injection volumes over a short
period should not exceed 2 ml, but if given slowly, up to 3 ml may be given at one time. When giving IV injections in the
rat, the small size of the vein makes drawing back to ensure placement ill-advised. A blood flash is rarely seen in the needle
hub. A small amount of substance should be injected before injecting the entire volume. If the tail vein blanches, then the
substance is placed intravenously.

Figure 6. Acceptable site for IP injection in the rat. A strict midline injection runs the risk of
puncturing the bladder or other structures. - To view this image in full size go to the IVIS website at
www.ivis.org . -
 Figure 7. Lateral tail vein. If the injection attempt is begun caudally, the vein is closer to the surface
and easier to access. - To view this image in full size go to the IVIS website at www.ivis.org . -

Subcutaneous (SQ) injections are best performed along the skin of the flanks or back. If animals are to be handled by the
scruff, injecting in that area is not recommended. SQ injection volumes may be up to 5 ml in larger rats. Per os (PO)
administration of known volumes of substances in the rat is best accomplished through oral gavage. Volumes of up to 5 ml
may be administered via gavage. Gavage in the rat is usually performed using a 15 or 16 gauge rigid metal gavage (or
feeding) needle. These needles have differently-sized bulbs at the tip, with smaller animals (under 75 g) using a 2 mm bulb
and larger animals (over 180 g) needing a 4 mm bulb. When accustomed to the procedure, rats do not object to gavage.
Care must be taken to avoid administering substances intratracheally. This is best accomplished by measuring the distance
to the stomach on the outside of the rat before attempting gavage, passing the needle to one side of the mouth (not
centrally), and watching the rat carefully for signs of trouble, such as struggling or injection solution appearing in the nose
or mouth. In many cases, animals may be trained to take oral formulations of drugs through being allowed to lick the
formulation from a syringe.

If an approximate dose of a compound to be given PO is acceptable, substances may be administered in the feed, water, or
in sweet-tasting treats. Although administration of drugs via water bottle is a commonly-performed practice, it can have
several pitfalls. In most cases, animals will initially reject the strange-tasting water, resulting in animals that not only need
treatment for a disease, but are now dehydrated. Some substances must be handled in certain ways (e.g., tetracycline should
be administered in a 5% sucrose solution for palatability, and the solution must be protected from light), and the length of
time that compounds remain active in aqueous solution may not be known. In addition, the animals will receive a dose
based on the amount of water they drink, not based on their weight or their need for the drug. This may prove problematic
when treating for diseases such as pinworms. Smaller animals may not be able to drink enough water to achieve an
effective dose. The same problems arise when compounds are administered via incorporation into feed. These routes
should only be used when the safety and efficacy of the compound is known and economies of scale make it the most
effective choice.

D. Euthanasia
In the 2000 Report of the American Veterinary Medical Association Panel on Euthanasia [11], several methods of
euthanasia are listed as acceptable for use in laboratory rodents. Rats may be euthanized through inhalation of carbon
dioxide, overdose of inhalant anesthetics, or overdose of barbiturates, either IV or IP. In a practice setting, there is very
little call for the use of the conditionally acceptable methods of decapitation and cervical dislocation. If cervical dislocation
must be used, it is best performed on rats under 100 grams. Larger rats are too muscular and will resist the procedure,
resulting in injury and distress to the rat and probably the handler.

IV. Surgery and Anesthesia

A. Anesthesia and Analgesia
Fasting the rat before anesthetic administration is not necessary. Rats are unable to vomit, which limits the risk of
aspiration pneumonia and have a high basal metabolic rate, which means they need to eat quite often. If rats must be fasted
for intestinal surgery, it is not necessary to fast longer than six hours. Metabolic support may be provided through the use
of sugar water [12]. Never water restrict a rat, as the effects of dehydration can be severe. Rats may be anesthetized using
injectable agents, or masked or intubated for the use of inhalant anesthetic agents. Injectable agents work quite well for
most rat procedures. Masking a rat down is not recommended, but induction in a box usually proceeds quite smoothly. If
intubation is desired for a longer procedure, the use of a 14 - 20 gauge catheter as an endotracheal tube, an otoscope, and a
guide wire will facilitate that procedure. Place the rat in dorsal recumbency and open the mouth. Use the otoscope to
visualize the larynx and place the guide wire in the trachea. Keep the wire in place while removing the otoscope. Thread
the catheter over the guide wire and then carefully remove the guide wire. Tie the catheter, using the hub, to the lower jaw.
Attach the catheter to the anesthetic machine. Due to the small tidal volume of the rat, minimization of dead space in the
anesthetic circuit is extremely important.
Analgesic agents are best administered to the rat through injections. The dose may be more precisely controlled in that
fashion, and the effects evaluated. Rats in pain exhibit certain characteristic behaviors. These include abdominal writhing,
falling or staggering when attempting to move, remaining hunched in the cage, and back arching [13]. Evaluation of rats
for these clinical signs postoperatively may indicate a need for more than perioperative analgesia. Since rats cannot vomit,
nausea in rats is evinced by pica. This behavior can be injurious to the rat. Monitor rats receiving opioids closely for this
behavior. Buprenorphine, although widely available, may not be suitable for use in rats as it is known to cause pica in some
strains of rats, most notably Sprague-Dawley rats [14]. See Table 8 for a formulary, including dosages for anesthetic and
analgesic agents.
 Table 8a. Formulary: Sedation and anesthesia [8,21-26].
Agent Dosage
Ketamine 50 - 100 mg/kg IM, IP
Xylazine 1 - 5 mg/kg IM, IP
Medetomidine 0.1 - 0.5 mg/kg IP, SQ
Acepromazine 2.5 mg/kg IM, IP
Atropine 0.05 mg/kg IP, SC
Diazepam 2.5 - 5.0 mg/kg IP, IM
Midazolam >5 mg/kg IP
Fentanyl/Droperidol 0.5 ml/kg IM
Pentobarbital 40 - 50 mg/kg IP, IV
Halothane Induction: 3 - 4%, Maintenance: 1 - 2%
Isoflurane Induction: 3 - 4%, Maintenance: 1.5 - 3%

Table 8b. Formulary: Injectable anesthetic cocktails [8,21-26].

Depth and duration of anesthesia Agent Dosage Agent Dosage
Surgical, 20 - 30 minutes Ketamine 75 mg/kg Medetomidine 0.5 mg/kg
Surgical, 20 - 30 minutes Ketamine 75 - 100 mg/kg Xylazine 10 mg/kg
Light, 20 - 30 minutes Ketamine 75 mg/kg Acepromazine 2.5 mg/kg
Light, 20 - 30 minutes Ketamine 75 mg/kg Diazepam 5 mg/kg
Light, 20 - 30 minutes Ketamine 75 mg/kg Midazolam 5 mg/kg

Table 8c. Formulary: Injectable agent antagonists [8,21-26].

Agent Antagonist Dosage
Fentanyl Butorphanol 0.4 mg/kg SQ
Fentanyl Naloxone 0.01 - 0.1 mg/kg IV, IM, IP
Xylazine, Medetomidine Atipamizole 1 mg/kg SQ
None specifically Doxapram 5 - 10 mg/kg IM, IV, IP
 Table 8d. Formulary: Analgesia [8,21-26].
Agent Dosage
Acetaminophen 110 - 305 mg/kg IP, PO
Aspirin 100 mg/kg PO
Buprenorphine* 0.05 - 0.10 mg/kg SC, IV BID
Butorphanol 2 mg/kg SC q 4 hours
Carprofen 5 mg/kg SC
Flunixin meglumine 2.5 mg/kg SC, IM BID
Ketoprofen 5 mg/kg SC
Morphine 2.5 mg/kg SC q 2 - 4 hours
1 - 4 mg/kg IV q 2 - 4 hours
* May cause pica in some strains of rat.

Table 8e. Formulary: Anti-infective agents [8,21-26].

Agent Dosage
Ampicillin 20 - 100 mg/kg daily or TID; PO,SC
Cephalexin 15 mg/kg SC; 60 mg/kg PO
Chloramphenicol 50 - 200 mg/kg TID; PO
palmitate
Enrofloxacin 2.5 - 10 mg/kg BID; PO or 10 mg/kg BID SQ
Doxycycline 2.5 mg/kg BID; PO
Fenbendazole 20 mg/kg daily x 5 d; PO
Griseofulvin 1.5% (15 mg/ml) DMSO solution, topically, 5 - 7 d
Ivermectin 200 - 400 µg/kg; PO, SC repeat in 8 - 10 d
For topical administration, dilute 1:100 in equal parts water and propylene glycol. Place
several drops between scapulae.
Metronidazole 20 - 60 mg/kg BID or TID, PO
1 ml of oral preparation in 150 ml drinking water *
Penicillin G 40,000 - 60,000 IU/kg BID, SQ, IM
Praziquantel 5 - 10 mg/kg; PO, SC, IM repeat in 10 d
Tetracycline 100 mg/kg SC (high dose); 5 mg/kg PO in drinking water**
Trimethoprim- 30 mg/kg BID-daily; SC, PO
sulfadiazine
*Rats may not tolerate the taste of metronidazole in their drinking water.
**Water may need to be sweetened with 5% sucrose. Water bottle should be protected from light and changed daily.

B. Surgery
In the laboratory setting, the most common surgery performed on rats is cannulation of the jugular veins. In practice, rats
may be castrated or spayed, and removal of mammary neoplasms in aged female rats is another common surgery. Suture
material used in rats is generally 4 - 0 or smaller. Rats do not tolerate skin sutures well, so all surgical closures should be
accomplished with tissue glue, surgical staples, or subcuticular closures. E-collars for rats and other small mammals are
commercially available, or they may be made for the rat using tape and radiography film.

Surgical support is critical in the rat. Due to their small size and high metabolic rate, they lose heat rapidly. Warming is
best accomplished through the use of recirculating water heating pads, but may also be accomplished using commercially
available "hand warmers" or surgical gloves filled with hot water. Care should be taken to avoid thermal damage to the
skin, regardless of the method used. Warm fluids may also be administered subcutaneously. During recovery, animals
should be kept warm and quiet. Since rats are exophthalmic, their eyes quickly become dry during surgery. The use of eye
lubricants during the surgical and postoperative period is important. Injectable anesthetic agents used in rats often have
prolonged sleep times, which means that animals may be asleep or groggy for over two hours. It is best if they are not
allowed to recover on loose bedding, since they may scratch their corneas or inhale or ingest particulate matter. Animals
should not be placed back into their cage or pen until they show signs of recovery.

C. Castration
(orchiectomy) is accomplished in the rat in the following manner: Place the anesthetized rat in dorsal recumbency. Prepare
the scrotum using standard surgical scrub techniques. Make a small (1 cm) median incision at the distal tip of the scrotum.
Clear the subcutaneous connective tissue, and then visualize the testes. If they are not readily apparent at the incision site,
apply gentle pressure to the lower abdomen to force them into the scrotum. Incise the muscular sac of the testes and expose
them by gently pulling on the cauda epididymis. Ligate the blood vessels and the vas deferens and remove the testis and
epididymis. Close the muscular sac with a suture, and close the skin with a wound clip. If an open technique is preferred,
the surgeon may close the inguinal rings. Closure is not necessary, however, as intra-abdominal fat seems to prevent the
formation of scrotal hernias.

D. Ovario-hysterectomy
in the rat is performed through a ventral midline incision. The abdomen is prepared in the standard manner. The abdominal
musculature and peritoneum are incised and the bicornuate uterus is visualized. The utero-ovarian artery is ligated and the
uterine vessels are ligated again immediately before the collateral blood supply to the cervix. The uterus and ovaries are
removed and the abdomen is closed in two layers, with the skin closed preferably with wound clips.

E. Removal of Mammary Neoplasms

in the rat is often a matter of the removal of an uncomplicated space-occupying mass. They are usually fibroadenomas, so
will often shell out of the skin easily. Since the masses may be allowed to become quite large before removal is considered,
closure of dead space caused by the removal of the mass will be a consideration. In addition, removal of the mass may
remove a significant amount of blood and fluid from the rat. Fluid support of the blood volume should be addressed if
necessary.

For a more detailed treatment of survival surgery in small rodents, please see the companion chapters in this volume:
Principles of Aseptic Rodent Survival Surgery: General Training in Rodent Survival Surgery - Part I and Principles of
Aseptic Rodent Survival Surgery: General Training in Rodent Survival Surgery - Part II by P. A. Brown and S.
Hoogstraten-Miller.

V. Diseases and Medicine

Infectious diseases in rats are often clinically silent. Weanlings and sucklings are most likely to show clinical
manifestations of disease processes. Often, evidence of many viruses known to infect rats is only detectable via serological
testing, usually by ELISA. See Table 9 for a list of agents for which research institutions and commercial rodent vendors
commonly screen animals. Readers of this chapter who work with laboratory animal facilities will be well-served by
perusing the chapter in this book on Quality Assurance/Surveillance Monitoring Programs for Rodent Colonies by J. D.
Reuter and R. C. Dysko. Practitioners can find commercial diagnostic laboratories that perform screening tests for these
diseases on the Internet or by contacting a local research university. In most cases, however, screening pet rats for this
"laundry list" of diseases is unnecessary. Most disease entities or clinical problems observed by practitioners treating pet
rats will likely be the result of accidents (trauma), husbandry-related deficiencies, or age-related changes. As noted above,
very few of the diseases listed in Table 9 will produce clinical signs. With regard to specific health conditions, skin
problems, gastrointestinal illnesses, and respiratory ailments are the most commonly seen. Some conditions related to
unique anatomic characteristics of the rat may also arise. Vaccinations are not normally given to rats and none are currently
approved for use in rodents. However, antibiotics and anthelmintics can be given safely to rodents. A formulary for rats is
provided in Table 8.
 Table 9. List of infectious agents for which research institutions and commercial vendors commonly screen.
Viruses Bacteria Parasites
Sendai virus Mycoplasma pulmonis Encephalitozoon cuniculi
Pneumonia virus of mice Cilia-associated respiratory bacillus Syphacia obvelata
S. muris
Rat coronavirus / Corynebacterium kutscheri Aspiculuris tetraptera
sialodacryoadenitis virus
Rat parvovirus Helicobacter hepaticus Hymenolepis
H. bilis (Rodentolepis) spp.
Kilham rat virus Salmonella spp. Heterakis spumosa
Toolan’s H-1 virus Streptobacillus moniliformis Trichuris muris
Reovirus type 3 Klebsiella pneumoniae Radfordia ensifera
K. oxytoca R. affinis
Rat enterovirus Pasteurella pneumotropica Myobia musculi
Lymphocytic choriomeningitis Pseudomonas aeruginosa Toxoplama gondii
virus
Hantavirus Staphylococcus aureus Polyplax spinulosa
Mouse adenovirus Streptococcus pneumoniae Ornithonyssus spp.
Streptococcus spp., beta hemolytic and Trichosomoides
Lancefield Grp B,G, spp. crassicauda
Pneumocystis carinii
Enteromonas spp.
Coccidia spp.
Trichomonas spp.
Giardia spp.
Spironucleus muris
Hexamastix spp.
Entamoeba spp.

A. Infectious Diseases
1. Respiratory Disease
Rats are prone to diseases of their respiratory tract. Rhinitis, bronchitis, and pneumonia can be attributed to one or more of
several agents known to infect rats: Mycoplasma pulmonis, cilia-associated respiratory (CAR) bacillus, sialodacryoadenitis
virus, and Sendai virus are four examples of agents that can cause respiratory illness in rats. Taken individually, these
agents may produce only a mild respiratory illness. However, these agents often occur concurrently and the disease process
is exacerbated. Pneumonia in rats is usually characterized by nonspecific signs, such as lethargy, weight loss, ungroomed
hair coat, and dyspnea. Rats sometimes exhibit snuffling or "chattering", a word used to describe moist rales audible to the
naked ear. Other agents known to complicate respiratory conditions in rats include Streptococcus pneumoniae, and
Corynebacterium kutscheri. Supportive therapy is indicated, and treatment may include antibiotics such as enrofloxacin,
tetracyclines, or cephalosporins. Rats ill with respiratory disease benefit from frequent cage changes which reduce high
levels of ammonia in the environment.

2. Sialodacryoadenitis Virus (SDAV)

SDAV is a coronavirus affecting rats. Infection is often subclinical in weanling or older rats, but suckling animals will
develop lower respiratory disease. The virus has a predilection for the salivary and lacrimal glands and affected animals
often exhibit a range of dramatic clinical signs. These may include nasal discharge, blepharospasm, epiphora, and
intermandibular swelling. As the infection resolves, the damaged tissues may take some time to become functional again.
Reduced tear output in the post-infective period often results in ocular sequelae such as corneal ulcerations, glaucoma, and
megaloglobus.

3. Diarrhea
Diarrhea is an uncommon finding in adult rats. However, suckling and weanling rats are prone to infections with several
viruses and bacteria that may result in diarrhea. In a previously uninfected colony, infection of young animals with
parvoviruses can cause diarrhea or steatorrhea, runted, jaundiced pups, and cerebellar hypoplasia. Although there are at
least three different strains of parvovirus, only one, Kilham’s rat virus, is associated with clinical disease. Salmonella (see
Zoonotic Disease section) and Tyzzer’s disease (see below) may also cause diarrhea in rats.

4. Tyzzer’s Disease
First discovered in 1917 by Tyzzer in Japanese Waltzing mice, this disease is caused by Clostridium piliforme, formerly
known as Bacillus piliformis, a spore forming anaerobic bacterium. It is transmitted horizontally through the fecal-oral
route. Animals that carry the bacterium are usually asymptomatic, but a clinical syndrome may be seen in recently weaned
rats. Nonspecific signs such as anorexia, lethargy, emaciation, ruffled fur, or sudden death without clinical signs may be
observed. Mucoid, bloody diarrhea may also be seen. On necropsy, animals may have megaileus. Many other organs,
including liver, cecum, colon, and heart, can have characteristic pathologic lesions. Histopathologic observation of bacilli
in target organs is diagnostic, and best obtained using a Warthin-Starry silver or Giemsa stain. There is no recommended
treatment other than supportive care. Antibiotics effective against Clostridia spp. may be used.

5. Ectoparasites
Ectoparasites are common in rats. They are usually diagnosed via skin scraping or adhesive tape impression of the pelt.
Mites such as Myobia musculi or Radfordia affinis are probably the most common ectoparasite in rats. Clinical signs may
include alopecia and pruritis, although infections may be asymptomatic. Treatment is with ivermectin given
subcutaneously, orally, or topically for two or three applications separated by 7 - 10 days. Fleas and lice may also be found
on pet rats, but they are less common. The University of Missouri’s Research Animal Diagnostic Laboratory is an excellent
source of photographs of the common endo- and ectoparasites of rodents and rabbits. Go to RADIL for a comprehensive
list. In addition, Parasites of Laboratory Animals, by Dawn Owen, has a number of high-quality photographs of ecto- and
endoparasites [15].

6. Endoparasites
Rats may host enteric parasites such as pinworms, Syphacia muris or Aspiculuris tetraptera, and less commonly, the rodent
tapeworms, Rodentolepis (Hymenolepis) nana or Rodentolepis (Hymenolepis) diminuta. Pinworms, due to the
environmental persistence of their ova, are a common problem in research institutions. Unless burdened with large numbers
of parasites, there are no clinical signs. Mild enteritis or rectal prolapse could be symptoms of a severe infection. Diagnosis
of Rodentolepis or Aspiculuris is by fecal flotation. Syphacia eggs are best seen using an adhesive tape impression of the
rectal area. ivermectin or fenbendazole are commonly used effective treatments for pinworm infections. ivermectin may be
administered topically, via subcutaneous injection, or in drinking water. Fenbendazole is best administered as part of a food
pellet. Effective treatment regimens for laboratory facilities usually involve either continuous feeding or two-week on/two-
week off 6 - 12 week regimens of anthelmintics, coupled with a rigorous environmental decontamination after the first
treatment. Piperazine, although less effective than either ivermectin or fenbendazole, may also be administered in drinking
water at a rate of 2 g/L [16]. Hemobartonella muris is an uncommon bacterial parasite that affects the red blood cells of
rats. It is transmitted by the spiny rat louse, Polyplax spinulosa and can cause anemia, weight loss, and dyspnea.

B. Noninfectious Diseases
1. Barbering
Patterned hair loss may be observed occasionally in group-housed rats. A dominant rat may chew the hair or whiskers of
the subordinate rat(s). The skin beneath the barbered hair is usually normal, and the dominant animal may be identified as
the only animal in the cage with no missing hair. Removing the dominant animal usually does little to correct the problem,
as another dominant animal may assume the behavior.

2. Dermatitis
Rats will typically spend much of their time grooming and when healthy, maintain a smooth, clean, fully haired coat.
Patches of hair loss can arise from behavioral anomalies such as excessive grooming, rubbing, or hair plucking. Some aged
or pregnant rats may also exhibit hair loss. Scratching or fighting may lead to wounds. These wounds are likely to become
secondarily infected with a staphylococcal or streptococcal organism. Secondary infections can be treated with topical
antibiotic ointments and clipping of the nails. E-collars may also aid in the treatment of dermatitis.
3. Conjunctivitis
Rats normally produce porphyrin-containing secretions from the Harderian gland (lacrimal gland), which is located behind
the eye. These secretions lubricate the eye and from there, drain into the nose. The gland constantly produces fluids, but
normal grooming removes them. When they are allowed to accumulate, they are sometimes mistaken for blood. The
condition known as chromodacryorrhea or "red tears" can be seen when the porphyrin-containing lacrimations or nasal
secretions accumulate around the eyes or nose. The appearance is not pathognomonic for any particular disease, but is often
a sign of stress, dehydration, or general malaise. One specific agent often associated with conjunctivitis in rats is
Pasteurella pneumotropica, which can be isolated from the nasopharynx, cecum, vagina, uterus, and conjunctiva.
Pasteurella infection is usually asymptomatic. Enrofloxacin is effective against Pasteurella in some cases.

4. Malocclusion
Rat incisors are hypsodontic, or open rooted. They continue to grow throughout the life of the animal. When the teeth are
not aligned for proper wear at the surface, they can grow to excessive lengths and cause significant trauma to the occlusive
surface of the mouth and surrounding tissues (Fig. 8). This is usually a problem of the incisors, not the molars.
Malocclusion can be inherited or be caused by trauma to the tooth root. Whenever a rat presents with anorexia or weight
loss, the teeth should be examined first to see if they are misaligned. Animals with this condition should have their incisors
checked every few weeks and trimmed, preferably with an electric burr to avoid loosening the teeth, which may occur if the
teeth are clipped. Molars cannot be managed in this way, and an animal with maloccluded molars may need to be
euthanized.

Figure 8. Malocclusion in a rat. Both the upper and lower incisors have continued to grow, resulting in
circular teeth that, in the case of the upper incisors, pierce the palate. - To view this image in full size
go to the IVIS website at www.ivis.org . -

5. Mammary Fibroadenoma
Tumors of the mammary glands are common in aged female rats. The majority of these are benign fibroadenomas that may
ulcerate or cause mechanical interference with locomotion of the rat. These tumors can often be successfully removed
surgically.

6. Megaloglobus
Megaloglobus is a pathologic enlargement of the globe of the eye of the rat due to various causes. These causes may
include a genetic tendency to retain the pupillary membrane or a viral infection, specifically sialodacryoadenitis virus, a
coronavirus. There is no known treatment, other than enucleation, for the condition, which is occasionally a finding in pets
or research animals. It is generally believed that there is pain associated with the initial development of the condition as
with some glaucoma-like diseases in humans. Rats have shallow eye sockets and normal handling of the rat may result in a
distressing (to the handler) protrusion of the eyes. Normal handling will not proptose the eyeball, however.

7. Myocardial Disease
In rats, myocardial disease is sometimes referred to as cardiomyopathy and is a common cause of death in older rats. The
heart is often enlarged, sometimes with pale streaks visible grossly. It is occasionally seen in animals less than six months
of age. Sudden death is often the first and only clinical sign observed.

8. Nutritional Deficiencies
Balanced rodent chows are readily available from many commercial sources. However, improper storage of these diets can
lead to degradation of minerals or vitamins that are sensitive to environmental temperature and humidity. Poor hair coat or
reduced reproductive performance could reflect dietary imbalance and may be addressed by replacing outdated or spoiled
feed.

9. Renal Disease
Hydronephrosis is often reported as an incidental finding in rats. It can vary from mild to severe dilation of the renal pelvis
and may also affect the ureter. Chronic progressive nephropathy is a common age-related disease of the rat kidney and can
be a cause of death in old rats. It is a progressive condition and usually more common in males than in females.
Nephrocalcinosis is also observed in rats. It is more common in females, and can be found in animals as young as 7 weeks.
It is characterized by the finding of calcium phosphate anywhere in the renal tissue, and can have an incidence as high as
50% in some strains of rats. Dietary restriction has been shown to reduce the incidence of renal disease as well as
myocardial disease in rats [17].

10. Retinal Degeneration

Albino rats are susceptible to retinal degeneration when they are exposed to light levels above 130 - 270 lux [18].
Recommended room light levels are 325 - 400 lux when measured at one meter above the floor [19]. When in doubt, albino
rats should be maintained at a distance from any direct light source, and the dark cycle of their photoperiod should be
maintained.

11. Ringtail
Ringtail is an uncommon finding in the rat. It is characterized by annular constrictions of the tail compromising circulation
and occasionally resulting in necrosis of distal portions of the tail. The cause is attributed to environmental factors such as
low ambient humidity. Efforts to experimentally reproduce the condition have been unsuccessful. There is no known
treatment. The condition is usually self-limiting, but amputation of necrotic portions of the tail may be necessary.

12. Urinary Calculi

Bladder stones are found in some older rats. The precise etiology is not well described, but genetics, imbalances in diet, and
unsanitary environmental conditions have all been implicated in their development. Urinary tract infections exacerbated by
wet or dirty bedding has also been linked to the formation of calculi. Calcium carbonate, struvite, carbonate-phosphate and
magnesium stones have all been recovered from the urinary bladders of rats.

C. Zoonotic diseases
Rats in the wild may carry many diseases and parasites communicable to humans. Rats may carry plague-bearing fleas,
typhus-bearing lice, or disease-bearing ticks. Like most small rodents, they are unlikely to carry rabies, however, being too
small to survive the attack of a rabid animal. It is relatively rare to observe these conditions in laboratory or pet rats. Some
zoonotic diseases that may be seen in captive rats are listed below. Check with your local public health authorities to
determine if any of these diseases are reportable in your area.

1. Allergic Disease
Rodents and rabbits are highly allergenic to many people, especially those with underlying atopic disease. The allergenic
proteins in rats are found in the urine. The protein, Rat n1, is a pheromone carrier and is found in higher levels in the urine
of male rats [20].

2. Hantaan Virus
There are many descriptive terms applied to a group of rodent-borne diseases caused by several viruses of the Hantavirus
group. In Southeast Asia, hantaviruses are associated with outbreaks of hemorrhagic and renal diseases. In June of 1993, a
newly recognized hantavirus was identified as the etiological agent of an outbreak of severe respiratory illness, Hantavirus
Pulmonary Syndrome (HPS), in the southwestern USA. It was contracted from exposure to deer mice. Cotton rats,
Sigmodon hispidus, and the rice rat, Oryzomys palustris, found mostly in the southern USA, have been associated with
hantaviruses that can cause illness and death in humans. Hantaviruses do not cause overt illness in their reservoir hosts.
Infected rodents can shed virus in saliva, urine, and feces for variable time periods.

3. Leptospirosis
Leptospirosis is caused by the bacterium Leptospira interrogans. Hosts include rats, mice, moles, gerbils, rabbits, hamsters,
cattle, and other mammals and reptiles. Leptospiral infections are rare in laboratory rats. The disease can vary in both
humans and animals from inapparent to severe infections and death. Organisms can be carried and shed in the urine for
long periods of time.

4. Ornithonyssus bacoti
O. bacoti is a mesostigmate mite, found rarely on laboratory rats. It is sometimes known as the tropical rat mite. Heavy
infestations of this blood-sucking mite could lead to general poor health, anemia, decreased reproductive efficiency, and
occasional deaths. It spends little time on the host so may be difficult to detect. In humans, the mite is associated with a
pruritic rash.

5. Rat Bite Fever

This human disease is caused by Streptobacillus moniliformisor Spirillum minus,which are nonpathogenic commensals
inhabiting the nasopharynx and respiratory tract of rats. These bacteria may also be present in the blood and urine of
infected rats and may be transmitted to humans via aerosols, fomites, and the bite of infected rats. In humans, there is a 3-
10 day incubation period and disease symptoms may include fever, vomiting, arthralgia, and rash. In humans, the disease is
treated with antibiotics, usually penicillin. Carrier rats are often euthanized.

6. Ringworm
As in other animals, ringworm in rats may be diagnosed by fungal culture and Wood’s lamp examination. It is usually
caused by Microsporum or Trichophyton spp. and can cause pruritis, alopecia, and scaling of the affected areas. Localized
topical treatment with several available antifungal agents or iodophor antiseptics has been shown to be effective.

7. Rodentolepis (Hymenolepis) nana

This tapeworm is found in the small intestines of rats, mice, hamsters, and primates, including man. R. nana can have a
direct or indirect (using grain beetles or fleas) life cycle. These cestodes are rarely found in laboratory rats and cause little
pathogenesis unless in severe infections. An infection with R. nana may be diagnosed by observing the eggs in a fecal
flotation or smear. Adult cestodes can also be seen on direct exam of the small intestine or the cysticercoid may be seen in
histopathology of the small intestine. Treatment of affected animals is not recommended due to the zoonotic hazard.

8. Salmonellosis
In the rat, salmonellosis is usually attributed to Salmonella enteritidis or S. typhimurium. Clinical signs in rats are rare but
may include lethargy, weight loss, conjunctivitis, poor hair coat, and soft stool or diarrhea, especially in sucklings or
weanlings. Diagnosis is by culture of the feces. Differential diagnoses include Tyzzer’s disease, rotavirus, enterococcal
enteropathy, cryptosporidiosis, or husbandry-related problems with feed, water, or bedding contamination. Since wild
rodents are often Salmonella carriers, pest control is recommended as a means of prevention. Treatment of affected animals
is not recommended since a chronic carrier state may result.

VI. Acknowledgements:
The authors would like to acknowledge the valuable assistance of Ms. Laura Casey in the production of the illustrations.

VII. Recommended Reading for the Practitioner and References

Recommended Reading
z Harkness JE, Wagner JE. The Biology and Medicine of Rabbits and Rodents. Baltimore, Maryland: Williams and
Williams, 1995.
z Hillyer EV, Quesenberry KE, eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. New York, New
York: WB Saunders, 1997.
z Merideth A, Redrobe S, eds. BSAVA Manual of Exotic Pets. Glouchester, England: British Small Animal Veterinary
Association, 2002.
Recommended References for the Researcher
z Krinke GG. The Laboratory Rat. In: G. Bullock and T. E. Bunton, eds. The Handbook of Experimental Animals. 1st
ed. San Diego: Academic Press, 2000; 756.
z Flecknell PA. Laboratory Animal Anesthesia: A practical introduction for research workers and technicians. 2nd ed.
London: Academic Press, 1996.
z Flecknell PA, Waterman-Pearson A. Pain Management in Animals. London: WB Saunders, 2000; 184.
z Fox JG, Anderson LC, Lowe FM, et al., eds. Laboratory Animal Medicine. 2nd ed. New York: Academic Press,
2002.
z National Research Council. Guide for the Care and use of Laboratory Animals. Washington, DC: National Academy
Press, 1996.
z Poole T, ed. The UFAW Handbook on the Care and Management of Laboratory Animals. 7th ed. Malden,
Massachussets: Blackwell Science, Ltd., 1999; 313-330.
z Sharp PE, La Regina MC. The Laboratory Rat. In: M.A. Suckow, ed. The Laboratory Animal Pocket Reference
Series. Boca Raton: CRC Press, 1998; 214.
z Waynforth HB, Flecknell PA. Experimental and Surgical Technique in the Rat. 2nd ed. London: Academic Press,
1992.
References
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