Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (2003) / Chapter Skim
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8 Agents and Treatments
8 Agents and Treatments
Pages 109-122
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From page 109... ...
, · determine how a chemical causes toxicity, to characterize the abuse liability of a new pharmaceutical, · determine whether an organism's response to a drug changes with chronic exposure and whether chronic exposure may lead to abuse or physical dependence, · examine a chemical that is known or hypothesized to have specific 109
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From page 110... ...
Additional information about behavioral tests that can be used to screen unknown drugs or genetic mutants is provided in Chapter 9. Situations requiring special housing or feeding arrangements were summarized in the earlier NIH report (NIH, 2002, p.
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From page 111... ...
In such studies, the dose available is varied across experimental conditions, and the rate of responding to obtain the dose, the number of drug deliveries obtained, and/or the amount of drug taken are the primary dependent variables of interest. In such studies, the likelihood that the animal will produce a fatal overdose is carefully considered in the design and choice of drug.
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From page 112... ...
Insertion of a cannula into a blood vessel, a body cavity, or the nervous system is another method of administering drugs. A permanently implanted cannula ensures that repeated injections can be given at precisely the same site and permits the study of drug effects without peripheral effects, such as pain at the injection site (Waszczak et al., 2002~.
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From page 113... ...
. Animal Care and Use Concerns Associated with Toxicity or Long-Lasting Drug Effects Some chronic drug experiments involve dosing that produces cumulative deleterious effects.
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From page 114... ...
ADDICTIVE AGENTS The previous section addressed a wide array of issues related to acute and chronic effects of various chemical agents, including drugs. This section extends that discussion by focusing on issues related to the testing of drugs that are of interest because their chronic use or exposure produces neuroadaptations thought to underlie the behavior patterns (such as tolerance and sensitization, dependence, and withdrawal)
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From page 115... ...
, and the presence of a stimulus previously paired with drug exposure (Siegel et al., 1982~. Animal Care and Use Concerns Associated with Chronic Exposure to Addictive Agents Studies of the effects of chronic exposure to addictive agents may involve prolonged or repeated exposure to high drug doses over a period of several days, weeks, months, or years.
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From page 116... ...
Nevertheless, even when the schedule of exposure to an addictive agent is designed to allow the expression of a withdrawal syndrome, consideration should be given to establishing contingencies in the event of life-threatening signs, such as excessive weight loss or protracted seizure. Such contingencies might involve supplementary administration of food or fluids through a feeding tube or treatment with an appropriate anticonvulsant drug.
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From page 117... ...
The startle response provides a basis on which to evaluate variables that influence auditory learning and perception. Auditory startle-reflex techniques also are used to evaluate effects of drugs and toxicants that may alter sensory function or response to unexpected stimuli (Crofton, 1992~.
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From page 118... ...
. If an experiment requires that animals live in the running wheel or in a cage that has been specifically modified to include a running wheel, the cage should comply with the space recommendations of the Guide.
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From page 119... ...
Animal-welfare issues include maintenance of an appropriate water temperature, and provision of proper care of the wet rodent after it is removed from the water, and the establishment of unambiguous humane endpoints for testing in the animal-use protocol (see "Mood-Disorder Models" in Chapter 9~. Animal Care and Use Concerns Neuroscience studies involving physical conditioning and exercise require appropriate attention to adaptation of the animal to the testing situation, its gradual conditioning to develop stamina, and close animal observation and record keeping during the exercise period.
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From page 120... ...
SLEEP DEPRIVATION Short-term sleep loss in humans typically has no adverse physiologic consequences other than increasing sleepiness and impaired performance in some tasks (Home, 1985; Naitoh et al., 1990~. Because sleep is a homeostatic process, adverse effects associated with short-term sleep loss are probably alleviated simply by providing the opportunity to "catch up" on sleep (Everson, 1997; Everson et al., 1989)
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From page 121... ...
Sleep deprivation of over 7 days with the disk-over-water system results in the development of ulcerative skin lesions, hyperphagia, loss of body mass, hypothermia, and eventually septicemia and death in rats (Everson, 1995; Rechtschaffen et al., 1983~. The duration of sleep deprivation must be well justified scientifically, particularly if it will be continuous for more than a few days.
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From page 122... ...
The use of automated sleep-deprivation devices, like the use of exercise devices, requires regular sanitation, good animal observation, and accurate record keeping.
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