fferent experimental paradigms. The chief animal welfare concern associated with anesthetized paralyzed animals is that the behavioral indicators of pain and/or distress are inhibited by NMBDs, and this makes it necessary to use special measures to monitor and regulate anesthesia (Gibbs et al., 1989). Anesthesia must be regulated in such a manner that it exerts either no effect or a minimal and constant effect on the neurophysiologic responses being measured. Of both animal welfare and scientific concern is the problem of monitoring and maintaining the animal’s physiologic state, particularly in experiments that extend over several days (Lipman et al., 1997). Issues can also arise regarding infection, in that it usually is not possible to conduct prolonged nonsurvival neuroscience experiments aseptically and the duration of these experiments is sufficient to allow infections to develop. A two-step paradigm is used in most prolonged nonsurvival neuroscience experiments. In one kind of study, during an initial step of 2–4 hours duration, the animal is surgically prepared for a subsequent data collection step, which follows immediately and can last for a few hours to several days (NIH, 1991). During the initial surgical preparation step, all procedures are completed under surgical anesthesia without NMBDs, and analgesics may be administered preemptively to augment the anesthetic regimen (see “Anesthesia and Analgesia” in Chapter 3). Other studies employ a variant of the two-step paradigm that involves performing, several days before the nonsurvival recording session, a survival surgery step during which various devices are implanted (such as a cranial pedestal and cham-
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ber that are used to secure the animal and the recording device, respectively) (NIH, 1991) (see “Multiple Survival Surgeries” in Chapter 4). The latter approach frequently allows the neuroscientist to perform the initial-survival surgery step with aseptic techniques in a dedicated surgical facility. Furthermore, only minor procedures (such as venipuncture and endotracheal intubation) are needed on the day of the prolonged nonsurvival recording session, and they can be performed with only light anesthesia augmented by analgesics. Following these minor procedures, general anesthesia is provided for the nonsurvival recording session. The difficulty involved in assessing whether paralyzed animals are free of pain and/or distress is acknowledged by the Guide, which states (p. 65): Some classes of drugs—such as sedatives, anxiolytics, and neuromuscular blocking agents—are not analgesic or anesthetic and thus do not relieve pain; however, they might be used in combination with appropriate analgesics and anesthetics. Neuromuscular blocking agents (e.g., pancuronium) are sometimes used to paralyze skeletal muscles during surgery in which general anesthetics have been administered (Klein, 1987). When these agents are used during surgery or in any other painful procedure, many signs of anesthetic depth are eliminated because of the paralysis. However, autonomic nervous system changes (e.g., sudden changes in heart rate and blood pressure) can be indicators of pain related to an inadequate depth of anesthesia. It follows that adequate anesthesia must be established and verified before the administration of NMBDs and initiation of the data-collection session. The animal should be maintained without NMBDs at a fixed anesthetic level until it is physiologically stable. It will take at least 30 minutes, depending on the duration of action of the anesthetics used during the initial surgical preparation period (if there was one), at a fixed anesthetic level and without change in physiological state to ensure that the animal is stable. That period should be used to establish and validate the physiological signs that will be monitored under paralysis to document that the animal is being maintained in a suitable condition. Experience has shown that care should be taken to ensure that the level of anesthesia established during this initial period is adequate but d