Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003) / Chapter Skim
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3 General Animal-Care Concerns
3 General Animal-Care Concerns
Pages 30-68
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From page 30... ...
Gaining consensus on the importance of training is easy; implementation and participation present challenges. Neuroscience research often involves situations in which the research team and the animal-care staff must work in close cooperation to optimize both animal welfare and research outcomes.
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From page 31... ...
The assessment of postprocedure pain, distress, and general health is a matter of subjective clinical judgment that depends on evaluating a variety of measures, including behavioral factors, and recognizing that the interpretation of these measures differs greatly among species; for example, some species mask pain or distress from the observer. However, how a trained animal performs a behavioral task can be a sensitive index of its general condition.
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From page 32... ...
For example, in some studies, the repeated application of an agent or a treatment might require multiple major survival surgeries. In such cases, the stress of undergoing general anesthesia repeatedly, the level of necessary asepsis, and the need to perform the procedures in a surgical setting may be special considerations.
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From page 33... ...
Second, regulatory responsibility for providing appropriate veterinary care rests with the veterinarian. Record keeping.
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From page 34... ...
because it minimizes the potential for the spread of disease through a shared scale, a reference weight is not needed to calculate a percentage of weight loss for assessment of health status, and body condition can be evaluated more rapidly than body weight. Neuroscience preparations can cause various degrees of debility that may be predictable in both severity and duration.
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From page 35... ...
Enlisting the animal-care group early to consider strategies that will meet basic needs and maximize well-being presents an opportunity to build a team approach. Generally, recovery from neurosurgery involves the same considerations as recovery from other surgical procedures.
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From page 36... ...
or animals with lesions of the labyrinth may be housed in the dark to prevent visual compensation for altered vestibular cues (Fetter et al., 1988; Zennou-Azogui et al., 1996~. In each of those types of neuroscience research, the animal protocol must ensure appropriate care and monitoring of the animal while maintaining the environmental requirements of the experiment; for example, food and water might be provided in the same locations before and after the lesion is produced.
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From page 37... ...
Interpreting the guidelines and regulations and applying them to a specific neuroscience procedure can be complicated, and it is important for all concerned to be cognizant of the relevant guidelines and regulations. The Guide states that: In general, surgical procedures are categorized as major or minor and in the laboratory setting can be further divided into survival and nonsurvival.
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From page 38... ...
All survival surgery will be performed using aseptic procedures, including surgical gloves, masks, sterile instruments, and aseptic techniques. Major operative procedures on non-rodents will be conducted only in facilities intended for that purpose which shall be operated and maintained under aseptic conditions.
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From page 39... ...
Neuroscience research often involves procedures that do not meet the strict definitions of major survival surgery given in the Guide and AWRs. Some procedures do not involve both penetration and exposure of a body cavity (for example, endoscopic surgery)
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From page 40... ...
In the absence of precedents for a particular minimally invasive procedure, consideration should be given to obtaining preliminary data from a pilot study performed under direct veterinary supervision and with appropriate reporting to the IACUC. Multiple Major Survival Surgeries In general, multiple major survival surgeries are discouraged, but they may be conducted if they are scientifically justified, related components of a research project approved by the IACUC (NRC, 1996~.
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From page 41... ...
This is especially encouraged for larger animals such as nonhuman primates. Administration of fluids is especially important for smaller mammals during lengthy surgical procedures because their ratios of surface area to body weight and higher metabolic rates necessitate nearly double the fluid supplementation necessary for larger mammals (Balaban and Hampshire, 2001~.
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From page 42... ...
General anesthesia produces a loss of awareness or consciousness and is used for surgical procedures or experiments that cannot be conducted in awake animals (NRC, 1992~. Examples of general anesthetics are inhalation anesthetics, such as isoflurane; opioids, such as fentanyl; and dissociatives, such as ketamine.
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From page 43... ...
. Studies have shown that preemptive analgesia (such as opiates, local anesthetics, or NSAIDs)
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From page 44... ...
. The AWRs state: All survival surgery will be performed using aseptic procedures, including surgical gloves, masks, sterile instruments, and aseptic techniques.
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From page 45... ...
A decision to allow major survival surgery to be performed in a modified laboratory setting should be contingent on the development of a set of stringent postsurgical monitoring and reporting procedures. For example, the IACUC may approve an exception to the Guide's recommendations subject to receiving a status report from veterinary staff on the health and welfare of animals during the postsurgical survival period, to ensure the efficacy of the various procedures proposed to mitigate the risk of postsurgical infection.
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From page 46... ...
The method of animal restraint used to achieve a particular objective in an experimental protocol should, according to the US Government Principles (IRAC, 1985) , be chosen so as to minimize distress to the animal.
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From page 47... ...
, or indirect, such as by remote video. The frequency of animal observation may depend on the specific experimental procedure, but it may also be determined by the species of animal, the degree and duration of restraint, the type of restraint device or technique, the stage of training of the animal to the restraint, and the animal's degree of habituation to the restraint.
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From page 48... ...
, personnel working with restrained animals should be trained in using the equipment properly and in handling the animals safely while causing them minimal distress. Wellqualified personnel will have a sound understanding of when restraint should be suspended or stopped if it compromises animal welfare.
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From page 49... ...
12~. Research protocols that use food or fluid regulation can be divided into at least three main categories: studies of homeostatic regulation of energy metabolism or fluid balance, studies of the motivated behaviors and physiologic mediators of hunger or thirst, and studies that regulate food or fluid consumption to motivate animals to perform novel or learned tasks (Toth and Gardiner, 2000~.
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From page 50... ...
, but the food or fluid consumption is not the experimental variable. In those studies, food and fluid regulation is used to motivate the animals to perform a specific behavioral task for a food or fluid reward; regulation of food or fluid outside the experimental session ensures response reliability to the food and fluid reward in each session (NIH, 2002~.
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From page 51... ...
Consideration of each of those details facilitates the establishment of interventional endpoints to maintain the animals' health and well-being. Food Regulation The Guide states that when the experimental situations require food or fluid regulation, at least minimal quantities of food and fluid should be available to provide for development of young animals and to maintain long-term well-being of all animals.
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From page 52... ...
Mechanisms for Mediation of Food Consumption on an Ad Libitum Diet There is individual variability in food intake and adult body weight (Toth and Gardiner, 2000~. Food intake may be regulated more by satiety than by hunger (Stricker, 1984~.
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From page 53... ...
When the latter method, referred to as restricted feeding, is used, a lower body weight also occurs. Both types of regulation cause a temporary increase in food efficiency in young rats, and the reduced intake is correlated with a reduction in the animal's relative fat content and an increase in relative water content (Brownlow et al., 1993~.
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From page 54... ...
. Fluid Regulation Physiologic Mechanisms of Fluid Consumption Three main physiologic stimuli mediate thirst, fluid consumption, and hydration in normal animals maintained on an ad libitum fluid-consumption schedule (Rolls and Rolls, 1981; Rolls et al., 1980; Stricker and Verbalis, 1988; Toth and Gardiner, 2000; Wood et al., 1982~.
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From page 55... ...
Determination of Minimum Fluid Consumption It is difficult to specify minimum fluid requirements for the various animal species, because there is a dearth of evidence in the scientific literature. That contrasts with the growing literature on the health consequences of caloric restriction.
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From page 56... ...
Fluid-Regulation Design When fluid regulation is selected as a behavioral motivator, access to fluid outside the experimental setting has to be regulated to motivate performance of the rewarded behavior (NIH, 2002~. Generally, fluid regulation is patterned after one of two designs.
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From page 57... ...
Efforts should be made to match an animal's typical watering schedules with circadian variables, because the risk to animals on fluid regulation is reduced if periods of access and total amounts available are appropriate to the species (NRC, 1995; Toth and Gardiner, 2000~. In addition to the behavioral aspects of fluid consumption, relationships between fluid intake and food intake should be considered.
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From page 58... ...
In both instances, nonhuman primates often supplement fluid consumption by licking water from cages after washing. Therefore, the assessment of each animal on a fluid-regulation protocol is prudent.
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From page 59... ...
However, if fluid regulation is determined to be the preferred method of motivating a particular behavior, consultation with veterinary personnel and a review of recent literature regarding animal training may be appropriate (NIH, 2002~. In training of a naive subject to perform a new task with a fluid regulation, gradual introduction to the concept that fluid availability is restricted or contextdependent (for example, earned while in the experimental apparatus)
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From page 60... ...
Variables that can be monitored to assess the nutritional or hydration status of experimental subjects include the following. Weight andfood intake Experimental animals on food or fluid regulation should be weighed several times a week, ideally before experimental sessions (NIH, 2002~.
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From page 61... ...
Regular observation of the quantity and qualities of the excrement produced by an animal on a fluid or food regulation provides information about both hydration status and physiologic compensation for fluid regulation. General appearance and demeanor and quality offer and skin Investigators and veterinary personnel share the responsibility for observing behavior, general appearance, and demeanor of experimental animals, which can be valuable indicators of their health status.
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From page 62... ...
Genetically modified animals are used to test hypotheses in several ways: the phenotype of the modified animal is evaluated to determine the pathogenesis of disease or gene influences on development, the modified animal is used to test interventions to treat its condition, or the animal is used as a tool to study the pathogenesis of other conditions. Transgenic Animals A transgenic animal has exogenous (foreign)
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From page 63... ...
genetic manipulation may be the only way to determine the precise role of the gene product particularly in behavior. The use of new inducible knockouts, in which the timing and placement of the targeted gene disruption can be controlled, will refine and extend the usefulness of genetically modified animals in neuroscience and behavioral research.
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From page 64... ...
Some genetically modified animals are created to develop a disease spontaneously, but others may develop a severe or debilitating disease even if the disease is not the intended outcome. Genetically modified animals are used in a wide array of experimental studies.
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From page 65... ...
Close scrutiny of genetically modified animals during routine daily observation by the animal-care personnel may be warranted. Animal-care personnel often discover disabilities and abnormalities in genetically modified animals (such
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From page 66... ...
Undetected health problems can also skew the assessment of more complex behaviors such as learning and memory, aggression, mating, and parenting, so it is essential to identify problems before behavioral phenotyping (see "Behavioral Screening of Genetically Modified Animals" in Chapter 9~. For mice, a general health assessment starts with a brief evaluation of body mass, core body temperature, and appearance of the pelage (fur)
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From page 67... ...
When a genetically modified animal strain has been characterized, the standard of "normal" for a mutant animal may or may not be the same as that for a nonmutant animal (ARENA-OLAW, 2002~; therefore, clinical signs that would be used as humane endpoints in normal animals may be inappropriate as endpoints in genetically modified animals. If the mutant phenotype does not affect the general welfare or clinical well-being of an animal, the same standard of "normal" may be used for mutant and nonmutant animals.
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From page 68... ...
Endpoint issues generally apply to the entire life of genetically modified animals. Therefore, endpoints become relevant both in the context of experimental procedures and with regard to the potential pain or distress that is caused by the genetic modification itself.
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