directly attributed to the presence of stress), and even less about those of distress. Thus, recognizing stress and distress in laboratory animals based on behavioral changes remains a significant challenge to investigators and animal care staff. A first-order approach to this challenge is to understand the animals’ normal behaviors, while keeping in mind that such behaviors are neither invariant nor universal. Although normal behaviors may sometimes be characterized simply by a lack of atypical behavior, such as stereotypic (i.e., repetitive) or self-injurious behavior, some species and strain differences are not always easy to discern, and further complications are introduced by gender, age, physiological state, genetics, and genetic modification of the animals. Furthermore, it is not possible to recreate the full range of species-specific behaviors in the laboratory setting, as some types of behavior (e.g., severe aggression) are clearly undesirable from a management perspective.

Physiological effects of stress are mediated through the endocrine, neural, and immune systems and changes in stress hormone levels such as cortisol as well as the actions of the autonomic nervous system in response to known stressors have been well documented. However, research has not necessarily focused on deciphering these complex mechanisms in situations of suspected distress.

Assessment for the presence of stress should consider conditions that reliably produce it (e.g., exposure to a predator) and may be based on clinical and biochemical parameters such as activation of the hypothalamic-pituitary-adrenal (HPA) axis, changes in other hormones (e.g., prolactin), and changes in blood pressure and heart rate, and behavioral measures. An effective assessment of distress is predicated upon solid knowledge of physiologic behavior for each species and careful observation. It should integrate information from multiple behavioral and physiological parameters and should involve a team approach that includes researchers, veterinarians, and animal caretakers/technicians, as distress levels will vary in relation to the species, husbandry conditions, and experimental protocol as well as with each individual animal. The Committee points out that although the differentiation between abnormal behaviors associated with or caused by stress/distress and those observed in disease states (for example, both distressed and sick animals may not clean themselves and have matted fur coat) may be conceptually difficult, poor health means poor welfare. It is the Committee’s opinion that, until more research is available, validated practices seeking what is best for the animals while maintaining the integrity of research protocols (i.e., the use of performance standards) should be used.

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