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Experimental Rat

Laboratory rats treated for up to 4 days with either selective COX2 inhibitors (rofecoxib, celecoxib) or nonselective COX inhibitors (diclofenac, flurbiprofen) showed a progressive reduction in sodium and potassium excretion (Harirforoosh and Jamali 2005).

From: Comprehensive Toxicology, 2010

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Protein

Inflammation

Experimental Animal

Experimental Mouse

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Occupational Health and Safety

Sanford H. Feldman, David N. Easton, in The Laboratory Rat (Second Edition), 2006

I. INTRODUCTION

Laboratory rats are one of the most commonly used species for biomedical research, second only to mice. Developing an adequate institutional animal care and use program requires that the institution's occupational health and safety program perform risk assessment at the interface between humans and rats. The human-rat interface must be characterized for the presence of risk agents that may adversely affect human health. Notable examples of risks that are intrinsic to the rat are its potential to inflict bite or scratch wounds, transmit zoonotic diseases, and shed allergens. Risk modifiers intrinsic to the human are determined by an individual's general health, immune competence, existing allergies, propensity to develop new allergies, and technical competence in handling laboratory rats. There are extrinsic factors introduced at the interface inherent to the experimental paradigm that may include administration of carcinogens, toxins, biological hazards, viral gene therapy vectors, radioisotopes and/or physical hazards (for example, electricity and laser light). There are ergonomic hazards for animal care personnel associated with the repetitive movements executed when performing animal husbandry leading to carpal tunnel syndrome and/or back strain. The design of buildings, animal facilities and animal caging can be engineered to mitigate the exposure of personnel to some risks inherent to working with laboratory rats.

Minimizing risks during human-rat interactions requires an overall assessment of risk agents and risk modifiers. Risk assessment requires determining the source and nature of the risk to humans, the frequency and duration of human exposure, and the intensity of the exposure. Risk assessment examines engineering controls and operational practices for their ability to minimize aerosol exposure and to limit the contact of humans to risk agents. Occupational risk of exposure is associated with provision of animal husbandry, cage washing activity, colony management, veterinary care, facility management and research activities. A comprehensive occupational health and safety program implements adequate controls at a variety of levels: administrative, physical plant engineering and maintenance, animal husbandry equipment, personal protective equipment and periodic assessment of employee health. Additionally, consideration must be given to second-hand exposure to non-research personnel to risk agents because of their job requirements (for example, facilities maintenance personnel, housekeeping personnel, administrative personnel) or by association with coworkers that passively transfer hazards on their soiled clothing, hands and equipment. The dynamics of how various administrative areas in an institution interact as part of a comprehensive rodent exposure program can be found elsewhere (National Research Council, 1997). The purpose of this chapter is to cover many of the risk agents to consider during development of an occupational health and safety program in a research facility that uses laboratory rats. It should be noted, however, that at this point in time specific pathogen-free laboratory rats are used in the vast majority of research in rats. Therefore, concerns regarding zoonotic disease transmission are almost exclusively associated with studies of feral rat populations or research purposefully inoculating rats with known biohazardous agents.

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Nutrition of the Laboratory Mouse

Merel Ritskes-Hoitinga, ... Lars Friis Mikkelsen, in The Laboratory Mouse (Second Edition), 2012

Introduction

Laboratory mice and rats have always made up a large percentage of the total number of animals used for biomedical research purposes. This percentage is usually around 80–90% of the total number of animals used. For this reason, these species have been well-characterized in many ways. The use of the laboratory mouse (Mus musculus) has increased even more dramatically over the last decades, due to the possibility of studying gene function in vivo by the use of genetic modification techniques which have resulted in many newly established mouse strains.

The nutrition of the laboratory mouse (and rat) has also been well-studied and well-defined in comparison with that of other species (for an overview see [1]). This chapter concentrates on important aspects of feeding laboratory mice. One needs to be aware of how nutrition and feeding as an environmental factor can interact with experimental results and animal welfare when nutrition is not the main focus of study. Moreover, when the mouse is used as an animal model for human nutritional conditions, specific experimental conditions need to be taken care of. This is important in order to obtain reliable experimental results and optimal welfare of the animals simultaneously.

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The Skin and Subcutis

Jyoji Yamate, in Boorman's Pathology of the Rat (Second Edition), 2018

3 Infectious Diseases

Laboratory rats used in toxicologic studies are kept under pathogen-free conditions and infectious agents should be absent. However, while the rats are kept under conventional conditions, infectious diseases may occur. Trichophyton spp. and Microsporum spp. dermatophytoses may infect rats. At the infected sites, alopecia, crusting, and dermatitis are seen, although most infections are subclinical. Dermatophytes are recognized as arthrospores and hyphae within the hair shafts of the infundibulum. Causative agents are readily stained with periodic acid Shiff (PAS). Rats are susceptible to Demodex infection The longitudinal mites are easily detected within the follicular infundibulum with perifollicular inflammation.

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Parasitic Diseases

David G. Baker, in The Laboratory Rat (Second Edition), 2006

I. INTRODUCTION

Laboratory rats may serve as hosts for a wide variety of parasites. Although most of these infections are clinically silent, some may result in severe disease. At the least, infections may affect host physiology, and therefore serve as unwanted variables in research. Consequently, only rats free of parasitic infections are entirely suitable as research subjects. Fortunately, advances in animal husbandry have resulted in a dramatic decline in parasitic infections in laboratory rats. This is particularly true for parasites requiring multiple hosts for completion of the lifecycle. In fact, parasites other than pinworms are uncommonly found associated with rats in the modern vivarium. However, wild rats may at times gain access to and contaminate animal facilities, as well as feed and bedding storage areas. Also, animal care personnel may privately and unknowingly purchase pet rats infected with parasites. Thus, the laboratory animal professional should be aware of those parasites capable of infecting the laboratory rat. This chapter reviews those parasites that may be found infecting laboratory rats. The information has been arranged primarily according to organ system(s) involved, and secondarily by parasite phylogeny. Each parasite is presented with a brief morphologic description, lifecycle, pathobiology, diagnosis, treatment, prevention, and control.

Treatment of parasite infections deserves a special word of caution. It is well known that many drugs used to treat parasitic infections or infestations have themselves the potential to alter host physiology. In so doing, these drugs may compromise the usefulness of research animals, including rats. Fortunately, the decline in prevalence of parasitic infections in laboratory rats has been accompanied by a decline in the use of parasiticides. However, the discovery of parasitic infection in laboratory rats will require action. At times, parasites may be removed chemically without affecting the usefulness of rats as research subjects. At other times, the needs of the research study will preclude the use of parasiticides, and necessitate non-chemical methods of parasite elimination, such as cesarean rederivation. To determine whether parasiticides are safe to use in specific situations, the laboratory animal professional should be aware of the physiologic effects of commonly used anti-parasitic compounds. Relatively few such agents are used to treat rats. Among those in use, thiabendazole has nonimmunosuppressive anti-inflammatory properties in rodents (Van Arman et al., 1975). Levamisole has been used as a broad-spectrum anthelminthic in both human and veterinary medicine. It has been shown to have numerous in vivo and/or in vitro effects on rats or rat cells. These effects include superoxide scavenging (Schinetti et al., 1984). antagonism of gastric ulcers caused by necrotizing and anti-inflammatory agents (Evangelista et al., 1984), enhancement of gastrointestinal absorption of some compounds (Utsumi et al., 1987), inhibition of platelet aggregation (Pinto et al., 1990), upregulation of pyruvate dehydrogenase and glycogen synthase activity in rat adipose tissue (Thomaskutty et al., 1993; Basi et al., 1994), inhibition of skeletal tissue mineralization (Klein et al., 1993). inhibition of fibroblast collagen synthesis (de Waard et al., 1998), decreased post-surgical translocation of bacteria (Cetinkaya et al., 2002), immune stimulation (Trabert et al., 1976), and others. Fenbendazole causes far fewer effects. In rats, these appear to be limited to subtle changes in behavioral performance in young rats from dams fed fenbendazole during pregnancy (Barron et al., 2000), although other minor effects have been demonstrated in other species. Albendazole, another benzimidazole with anthelminthic properties, is embryotoxic in rats, induces drug-metabolizing enzymes in the liver (Souhaili-el Amri et al., 1988), and delays rat brain microtubule assembly (Solana et al., 1998). Lastly, ivermectin, a macrocyclic lactone disaccharide and member of the avermectin anthelminthic family, is not without its effects on rat physiology. This is important considering the common use of ivermectin in the treatment of parasitic infections in rats and other host species. In rats, ivermectin and doramectin, another avermectin, are known to possess anxiolytic effects (de Souza Spinosa et al., 2000, 2002). Still other members of the avermectin family may be selectively cytostatic against tumor cells (Driniaev et al., 2001). Lastly, the avermectins may cause developmental neurotoxicity in rats (Poul, 1988; Wise et al., 1997). Each of these reports highlight the potential for commonly used anthelminthics to alter host physiology.

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Norbormide

L.P. Weber, in Encyclopedia of Toxicology (Third Edition), 2014

Animals

Laboratory rats showed difficulties in locomotion and ataxia but no hind limb paralysis after treatment with norbormide. Death occurs within 15 min to 4 h after struggling, dyspnea, hypothermia, and convulsions. Oral lethal dose 50% (LD50) values for Norway rats ranged from 5.3 to 15 mg kg−1. Rodents other than rats have considerably higher oral LD50 values (e.g., hamster, 140 mg kg−1; guinea pigs, 300 mg kg−1; and mice, 1000–2250 mg kg−1). However, no effect was detected with 1000 mg kg−1 doses of norbormide in dogs, cats, monkey, sheep, pigs, chickens, mallard ducks, and prairie dogs. Interestingly, L-type voltage-dependent calcium channels in guinea pig heart were relatively selectively inhibited by norbormide in the sinoatrial and atrioventricular nodes, suggesting a possible therapeutic benefit for norbormide in treating supraventricular arrhythmias in heart failure.

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Taxonomy and Stocks and Strains

Hans J. Hedrich, in The Laboratory Rat (Second Edition), 2006

Publisher Summary

The laboratory rat has long been used in experimental physiology and has made significant contributions to several complex areas of mammalian biology. This chapter presents the taxonomy of laboratory rat and discusses its stocks and strains. Rats are rodents, and thus members of the largest family of mammals. Approximately 1,325 living species of murid rodents have been described by now, the members of which are currently placed in 281 genera distributed among 17 subfamilies, and which include most of the familiar rats and mice. Stocks and strains of laboratory rat discussed in the chapter are outbred stocks and inbred strains including standard inbred strains, coisogenic and congenic strains, consomic strains, and recombinant inbred strains. A key feature of rat nomenclature is the laboratory registration code, whether it is for the definition of an outbred stock or an inbred strain. This code is usually three to four letters, and identifies a particular producing institute, laboratory, or investigator. Further, these codes are intended to identify outbred stocks and inbred strains, including congenic strains.

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The Alarm Phase and the General Adaptation Syndrome

R. McCarty, in Stress: Concepts, Cognition, Emotion, and Behavior, 2016

Sensitization

When laboratory rats are exposed to a high-intensity stressor, there are recurring alterations in cardiovascular and metabolic homeostasis. One such stressor that has been studied is immersion of laboratory rats in water maintained at 18 or 24 °C for 15 min per day for 27 consecutive days. When compared to controls exposed to swim stress for the first time, animals exposed to chronic intermittent swim stress had significantly greater elevations in plasma levels of NE and EPI. This sensitized response of the sympathetic-adrenal medullary system to chronic intermittent swim stress is dependent on stressor intensity (i.e., water temperature). In contrast, chronic intermittent swim stress in water at 30 °C results in habituated plasma catecholamine responses.

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Developmental Neurotoxicity of Abused Drugs

Brian J. Piper, Jerrold S. Meyer, in Reproductive and Developmental Toxicology (Second Edition), 2017

Species Considerations

Laboratory rats (Rattus norvegicus) and mice (Mus musculus) are the most commonly used animals in developmental neurotoxicity studies involving drugs of abuse. Both species are relatively inexpensive, can be bred readily in the laboratory, and have a short gestation period and rapid postnatal development. Investigators using rats or mice can avail themselves of an enormous existing literature on fetal development, neuroanatomy, neurochemistry, molecular genetics, and behavioral characteristics of both the animals. Genetic engineering of mice affords an additional powerful tool to examine mechanisms of developmental neurotoxicity, although this approach has not yet been fully exploited by the field. Despite all the important advantages of using a rodent as opposed to a primate animal model, there are also a few disadvantages that should be kept in mind. First, as mentioned earlier, rodents are not as suitable as primates for testing higher cognitive functions. As Paule et al. (1990) have elegantly demonstrated, it is possible to design cognitive test batteries that directly probe the same functions in monkeys as in children, and such test batteries have been used to investigate the effects of prenatal exposure to drugs of abuse and other potential toxicants on cognitive function (Morris et al., 1996). Second, because development is so much more rapid in rodents than in humans, it is necessary to adopt an appropriate translational approach in selecting the period of drug administration for modeling human gestational exposure. Early methods for equating brain maturation in rodents (mainly rats) to that of humans relied primarily on neuroanatomical comparisons at specific points in fetal or postnatal development (Clancy et al., 2001, 2007a). However, Clancy et al. (2007b) have now developed a web-based neuroinformatics approach to the extrapolation of brain development across 10 different species: hamsters, mice, rats, rabbits, spiny mice, guinea pigs, ferrets, cats, rhesus monkeys, and humans. The computational algorithms use days post conception as the time measure, and separate extrapolations are provided for cortical development, limbic system development, and development of noncortical/nonlimbic brain areas. For example, 20 days post conception in mice (equivalent to roughly 1 day postpartum in this species) translates to approximately 124, 90, and 97 days post conception for the development of cortical, limbic, and noncortical/nonlimbic brain areas, respectively, in humans. Consequently, administering a drug of abuse to newborn mice can be expected to influence neurodevelopmental events that occur during the second trimester of human pregnancy.

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