Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003) / Chapter Skim
Currently Skimming:
9 Behavioral Studies
9 Behavioral Studies
Pages 123-149
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 123... ...
Behavioral measures are also used often to detect or measure changes in brain function that may be produced by disease, neural injury, genetic modification, or exposure to various agents and treatments. The purposes of this chapter are to address several general issues that arise in behavioral studies and to give more detailed consideration to a few specific aspects of neuroscience research in which the measurement of behavior is a central feature.
|
From page 124... ...
For example, in certain behavioral procedures, rats and monkeys have been shown to engage repeatedly in behaviors that produce exposure to electric shock, an event commonly assumed to be an aversive (Brown and Cunningham, 1981; Cunningham and Niehus, 1997; Cunningham et al., 1993; Kelleher and Morse, 1968~. Thus, under these experimental conditions, electric shock would be labeled an appetitive stimulus, not an aversive one.
|
From page 125... ...
Because brain mechanisms underlying the different types of learning may differ, the decision to present appetitive and aversive events in a response-contingent or response-noncontingent manner should be based on the scientific goals of the study. Rationales for Using Appetitive and Aversive Stimuli Appetitive or aversive stimuli are typically used to motivate an animal to perform a particular behavior.
|
From page 126... ...
As noted earlier, selection of the specific motivational stimuli in a task may be influenced by limitations imposed by the recording techniques; for example, an event that produces little or no movement in an animal may be preferred in sensitive physiologic recording procedures. In some situations, choice of a motivational stimulus and its characteristics will be guided by previous research showing that variability in response to it is low, thus reducing the number of animals that must be used in the procedure.
|
From page 127... ...
For example, the scientific goals of investigators interested in the neural bases of learning and memory or the mechanisms underlying a specific type of motor behavior might be accomplished by using a broad range of appetitive or aversive events. In situations where the scientific rationale for the choice of a particular motivational stimulus is not compelling or the IACUC is unsure whether one stimulus produces more or less overall discomfort or distress than another (e.g., mild electric shock versus a food pellet combined with food restriction)
|
From page 128... ...
Moreover, consideration must be given to drying the animal and providing access to an appropriate heat source (unregulated heating pads and heat lamps should be avoided as they can develop hot spots and cause thermal burns) after water exposure to prevent hypothermia.
|
From page 129... ...
Behavioral screening tests differ from hypothesis-driven experiments in that screening tests assess multiple behavioral measures because there is little information to indicate what important effects might be observed. Screening also is used if limitation of time and resources require a test that can be administered quickly to a number of animals.
|
From page 130... ...
Finally, if the experiment permits removing the nonhuman primate from its home cage to a special test apparatus (see "Restraint" in Chapter 3) , video cameras can be used to remotely monitor nonhuman primates while they are in the special test apparatus (Ro et al., 1998~.
|
From page 131... ...
TABLE 9-2 Functional Observational Battery for Pre- and Post-weanling Rats Endpoint Measurement/Scale Body Weight Open-Field Rearing Gait Score (and description of gait) Forelimb Grabbing Surface Righting Response Open-Field Activity Arousal Handling Reactivity Tremorigenic Score Urination/Defecation Lacrimation Salivation Tail-Pinch Response Click Response g number 1 to 3 1 to4 1 to4 1 to6 1 to5 1 to4 1 to 3 1 to5 1 to 3 1 to 3 1 to5 1 to5 SOURCE: Moser, 2000b.
|
From page 132... ...
Behavioral Screening of Genetically Modified Animals General Considerations Once a general health assessment of a newly developed strain of genetically modified animals is completed (see "Genetically Modified Animals" in Chapter 3) , behavioral phenotyping should proceed as soon as sufficient numbers of transgenic animals are available to identify sensory, motor, or motivational deficits that may compromise animal well-being.
|
From page 133... ...
Dramatic behaviors that include increased aggression, altered maternal care, decreased sexual behaviors, seizures, and impaired motor coordination and sensory abilities are commonly reported for knockout mice (e.g., Barlow et al., 1996; Brown et al., 1996; Brown et al., 2000; Chen et al., 1994; Crawley, 2000; Nelson et al., 1995; Saudou et al., 1994~. Presumably, knockout mice may have more subtle behavioral changes that have not yet been discovered, even among mutants with no obvious behavioral phenotypes.
|
From page 134... ...
Pain sensitivity can be tested with paw removal from a hot plate or a tail-flick test (Rubinstein et al., 1996~; the motor skills of transgenic mice should be assessed before this test to avoid tissue damage caused by slow reaction, rather than high pain thresholds, but in any case, the stimulus should always be terminated after a predetermined time interval selected to avoid tissue damage. The proposed procedures for assessing general motor skills in transgenic mice before behavioral testing and the criteria for early removal of an animal from a potentially painful or distressful stimulus should be described in detail in the animal-use protocol.
|
From page 135... ...
Other exploration-based tests of anxiety include the elevated plus maze, the light-dark exploration test, the emergence test, and the free-exploration test (Belzung and Griebel, 2001; Pare et al., 2001~. The elevated plus maze has become the most commonly used screen for novel anxiolytics, as well as a probe for anxiety in transgenic mice (Holmes, 2001~.
|
From page 136... ...
For example, the circular platform maze or radial arm maze described earlier will be better choices than a water maze for testing cognitive function in mice with severe motor impairments that interfere with swimming. Because screening procedures often involve testing a given animal in multiple tasks, excellent record keeping practices are imperative.
|
From page 137... ...
that the animal might perceive as threatening or stress-inducing. Behavioral Training Experiments on awake, behaving animals generally occur in several stages.
|
From page 138... ...
Aversive procedures generally involve exposing animals to some form of noxious stimulus (such as mild electric shock, a bitter food, or an unpleasant sound) when they make an incorrect behavioral response.
|
From page 139... ...
Accordingly, records often include details regarding the animal's performance on the behavioral task and various physiologic indexes. Documentation and Record Keeping Because of the potential health implications of food or fluid restriction, the health status of animals used should be well documented if food or water availability is restricted.
|
From page 140... ...
recommend that: If task performance is not adequately supporting minimal intakes, the experimenter should re-evaluate and perhaps simplify the training strategy to facilitate the animal's ability to learn and master the task. Standard clinical tests will reveal serious pathologic conditions, but the more insidious, gradual deterioration of an animal's status can be recognized and treated only if there is regular observation and the implementation of professional judgment.
|
From page 141... ...
This test avoids some of the problems of locomotion and coordination of the Porsolt test, but if the targeted gene affects metabolism or food intake, its reliability for depressed behavior may be impaired. In all those behavioral tests of depression, proposed procedures for monitoring, record keeping, and humane intervention should be described in the associated animal-use protocol and approved by the IACUC.
|
From page 142... ...
Animals should be dried thoroughly after the swim test, and it is advisable to place their cages on a heating pad for several minutes. The use of unregulated heating pads or heat lamps should be avoided as they can develop hot spots and cause thermal burns.
|
From page 143... ...
Social Disruption Social disruption can be used as an experimental technique in neuroscience and behavioral research, but it can also be an inadvertent confounder of the research. Experimental designs that purposefully incorporate social disruption, do so through the temporary removal and reintroduction of offspring or of group or pair-mates, longer-term or repeated reorganization of social groups by removal of group members or by introduction of unfamiliar animals to groups or to one another, or even the merging of different groups of animals.
|
From page 144... ...
Self-injurious behaviors, stereotypic behaviors, extreme timidity or aggressiveness, and inability to mate or provide adequate care to offspring are maladaptive behaviors that might result from the social disruption (NRC, 1992~. Kittens separated from their mothers at an early age tend to be more aggressive and nervous as adults (Seitz, 1959)
|
From page 145... ...
, and steps should be taken to minimize this distress if it is an unintended byproduct of the experiment. The offspring of animals in social disruption experiments may also be impacted by the maladaptive behavior of its dam.
|
From page 146... ...
Because pain and injury to both the prey animal and predator are significant welfare issues with these kinds of studies, methods to protect the prey animal from physical attack or modeling elements of the predation sequence should be considered (Novak et al., 1998b)
|
From page 147... ...
Environmental Deprivation Animals may be exposed to nonsocial behavioral stressors to determine their effects on neural and neuroendocrine function. For example, animals may be restrained for brief or for sustained periods by being held, tethered, chaired, or immobilized by other restraint devices or placed in small enclosures or wrappings that restrict movement.
|
From page 148... ...
Exposure to intense, repeated, or prolonged stressors can have a variety of adverse effects, including suppression of reproduction, immune dysfunction, cardiovascular and gastrointestinal impairment, and persistent disruption of neuroendocrine function (Moberg and Mench, 2000~. One consequence of exposure to behavioral stressors may be the development of abnormal behaviors, including self-mutilation, mutilation of other animals (such as tail-biting in pigs and cannibalism)
|
From page 149... ...
BEHAVIORAL STUDIES 149 mining when to end a test early to avoid unnecessary pain and/or distress. If little or nothing is known about the possible outcomes of exposure to a particular behavioral stressor, IACUC review and approval of the protocol may involve a requirement to conduct pilot studies, mandatory oversight of initial testing by veterinary staff, or provision of regular progress reports as a condition of continuing approval.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.