Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003) / Chapter Skim
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2 Protocol-Development Strategies
2 Protocol-Development Strategies
Pages 12-29
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From page 12... ...
Developing an animal care and use protocol is a negotiation among the PI, the veterinarian, and the IACUC to balance animal well-being with the experimental goals. By involving all parties early in the protocol-development process, particularly for protocols that involve extensive experimental manipulation or difficult to maintain animal models, the PI can help to prevent misunderstandings and delays while facilitating IACUC review and approval.
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From page 13... ...
The veterinary staff has the legal responsibility for animal care. Veterinary medical care is best administered with consideration for the scientific goals of the study.
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From page 14... ...
The novelty or unpredictable nature of the experimental techniques or animals being investigated in pilot studies warrants heightened awareness of animal care and welfare. An important goal for pilot studies should be the collection of the maximal amount of useful preliminary information, and a team effort and team approach will be key factors in reaching the goal.
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From page 15... ...
It should be noted that using a more sophisticated experimental design and statistical analysis provides more power to detect an effect (Dell et al., 2002~. Some aspects of neuroscience research (such as developing and producing genetically modified animals)
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From page 16... ...
The term distress encompasses the negative psychologic states that are sometimes associated with exposure to stressors, including fear, pain, malaise, anxiety, frustration, depression, and boredom. These can manifest as maladaptive behaviors, such as abnormal feeding or aggression, or pathologic conditions that are not evident in behavior, such as hypertension and immunosuppression (NRC, 1992~.
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From page 17... ...
consumption; does not make nest; hiding tremors Rabbit Head pressing; teeth grinding; Excessive salivation; Rapid, shallow may become more aggressive; hunched posture respiration; increased vocalizations; decreased excessive licking and scratching; food/water reluctant to locomote consumption Dog Excessive licking; increased Stiff body movements; Decreased aggression; increased reluctant to move; food/water vocalizations, inclusive of trembling; guarding consumption; whimpering, howling, and increased growling; excessive licking and respiration scratching; self-mutilation rate/panting Cat Hiding; increased vocalizations, Stiff body movements; Decreased inclusive of growling and hissing; reluctant to move; food/water excessive licking; increased haircoat appear rough, consumption aggression ungroomed; hunched posture; irritable tail twitching; flattened ears Nonhuman Increased aggression or Stiff body movements; Decreased Primate depression; self-mutilation; often reluctant to move; food/water a dramatic change in routine huddled body posture consumption behavior (e.g., locomotion is decreased) ; rubbing or picking at painful location aNO single observation is sufficiently reliable to indicate pain; rather several signs, taken in the context of the animal's situation, should be evaluated.
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From page 18... ...
Acceptable levels range from an animal's pain threshold to its pain tolerance level. Pain threshold is the stimulus level at which pain is first perceived, while pain tolerance is the highest intensity of painful stimulation that an animal will voluntarily accept.
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From page 19... ...
Maladaptive behaviors include persistent attacks on the perceived source of the pain, self-mutilation at the injured or stimulated site, and a state of learned helplessness in which the animal gives up and no longer attempts to escape, avoid, or control the stimulus. To avoid the development of maladaptive behaviors and to minimize pain during experimental manipulations where the animal is denied control of the stimulus, it is critical that the neuroscientist attempt to define the level of pain produced by the stimulus (Dubner, 1987)
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From page 20... ...
Severe chronic pain can reduce body temperature, cause a weak and shallow pulse, and depress respiration. As noted above, animals cannot control chronic or persistent pain, and it is important to assess the intensity of the pain by using behavioral measures.
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From page 21... ...
They include implanted radio transmitters to measure autonomic nervous function, microdialysis techniques for sample collection, remote blood sampling methods, biosensors for recording central nervous system responses in
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From page 22... ...
The selection of a general anesthetic should reflect professional judgment as to which anesthetic best meets the clinical and humane requirements without compromising the scientific aspects of the research protocol (NRC, 1996~. That sufficient anesthesia has been provided can be ensured by monitoring reflexive responses to painful stimuli, respiration, pupil size, stability of heart rate and blood pressure or electroencephalographic activity.
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From page 23... ...
and should be inherent in the animal-use protocol design. USING ANIMAL BEHAVIOR TO MONITOR ANIMAL HEALTH Animal behavior can be an excellent measure for assessing overall health, indeed, the clinical signs used to diagnose disease in animals are often based on behavior (for example, signs of pain)
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From page 24... ...
General categories of endpoints include biologic markers, such as the development of paralysis in models of neural tumors (Huang et al., 1993, 1995~; markers of therapeutic failure, such as persistent signs of tumor growth despite drug intervention; markers of disability, such as inability to stand in models of bacterial endotoxemia (Krarup et al., l999~; markers of disease exacerbation, such as increased seizure frequency; and general markers of clinical deterioration, such as substantial changes in body weight, alertness, respiration, and body temperature (Redgate et al., 1991; Toth, 1997~.
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From page 25... ...
However, in the second instance, if the onset of disease symptoms was used as a humane endpoint, the animal would never develop the disease, the treatment could not be tested, and the scientific goal of the study could never be realized. Humane endpoints may sometimes seem incompatible with experimental endpoints, because ending an experiment for humane reasons can interfere with achieving the scientific goals of the study.
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From page 26... ...
The frequency of observations depends on the nature of the experimental manipulation or disease state and the expected rate of change in an animal's condition. In some cases, such as genetically modified animals, unpredicted or unintended alterations may occur that adversely affect animal well-being (Stokes, 2000~.
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From page 27... ...
However, a recent study suggests that witnessing decapitation may be no more disruptive to Sprague-Dawley rats than other common procedures, such as cage changing, restraint, and injections (Sharp et al., 2003~. Methods of euthanasia that are commonly used in neuroscience research include decapitation, cervical dislocation, carbon dioxide inhalation, and barbiturate overdose.
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From page 28... ...
, has adverse consequences in terms of the validity of the experimental design and interpretation of the resultant data. Because anesthetic and sedative agents exert their effects by altering brain function, use of these agents can alter the concentrations, production, or activity of structures or substances that are being examined to answer an unrelated scientific question (for example, Kasten et al., 1990; Mills et al., 1997; Savaki et al., 1980~.
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From page 29... ...
The basic elements of such a program include procedures and training in dealing with potential exposures, the required use of protective equipment, and access to medical professionals who are knowledgeable about B virus (AAALAC, 2002; CDCNIH, 1999~. Compliance with institutional occupational health and safety requirements should be a prerequisite for IACUC approval of an animal-use protocol and should be evaluated carefully by the IACUC during its semiannual inspections.
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