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5 Prolonged Nonsurvival Studies Most prolonged nonsurvival studies are carried out in anesthetized animals and extend over many hours or days. In a prolonged nonsurvival study of the visual system, the scientific needs of the experiment usually require that stationary images or images whose motion can be controlled accurately and repeatedly be presented to the retina, so self-generated movements by the animal must be minimized. Minimizing self-generated movements is also required in other neuroscience studies. Neuroscientists frequently resolve this problem by administering neuromuscular blocking drugs (NMBDs) that paralyze all voluntary muscles, including the extraocular muscles (Flecknell, 1987; Hildebrand, 1997). Many of the typical indicators of anesthetic depth (such as response to noxious stimuli and changes in respiratory rate) are thus eliminated, and this makes it difficult to assess whether an animal is experiencing pain and/or distress. But that assessment is critical, both for the welfare of the animal and to avoid compromising experimental results (Moberg, 1999). An earlier workshop on anesthesia and paralysis in experimental animals (Anonymous, 1988) considered the special problems associated with this approach, and they are also discussed in Preparation and Maintenance of Higher Mammals During Neuroscience Experiments (NIH, 1991), the predecessor of the present document. Without exception, the scientific need to use NMBDs must be explained in an investigator’s animal-use protocol and approved by the IACUC (NRC, 1996). Principle V of the US Government Principles (IRAC, 1985) states that “surgical or other painful procedures should not be performed on unanesthetized animals paralyzed by chemical agents,” and the Guide further states (p. 65): Neuromuscular blocking drugs . . . do not provide relief from pain. They are used to paralyze skeletal muscles while an animal is fully anesthetized. They
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might be used in properly ventilated conscious animals for specific types of nonpainful, well-controlled neurophysiologic studies. However, it is imperative that any such proposed use be carefully evaluated by the IACUC to ensure the well-being of the animal because acute stress is believed to be a consequence of paralysis in a conscious state and it is known that humans, if conscious, can experience distress when paralyzed with these drugs (NIH, 1991; NRC, 1992). The special concerns associated with prolonged nonsurvival experiments were well summarized in Preparation and Maintenance of Higher Mammals During Neuroscience Experiments (NIH, 1991): The most critical issues in prolonged nonsurvival experiments arise in the context of anesthesia, maintenance of physiological state, and monitoring of the animal’s condition. The choice of anesthetic must jointly satisfy the need of the experimenter to perturb the preparation as little as possible and his/her obligation to ensure that the animal remains free of pain and distress. Maintaining an anesthetized (and often immobilized) animal in sound physiological condition for several days is a considerable challenge and monitoring both the anesthesia and the animal’s general condition requires careful attention to a number of kinds of measurement. A variety of experimental protocols have been used to minimize the difficulties. The Guide should be interpreted as a flexible document in reviewing protocols of this sort, because procedures may vary with species and among di