Physiology & Behavior 68 (2000) 501–507 0031-9384/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0031-9384(99)00203-6 Animal models of disease P.M. McCabe a, *, John F. Sheridan b , J.M. Weiss c , J.P. Kaplan d , B.H. Natelson e , W.P. Pare f a Department of Psychology, University of Miami b Ohio State University Health Sciences Center, Columbus, OH, USA c Emory University School of Medicine, Atlanta, GA, USA d Wake Forest University School of Medicine, Winston–Salem, NC, USA e VA Medical Center, East Orange, NJ, USA f VA Medical Center, Perry Point, MD, USA Received 23 June 1999; accepted 19 October 1999 1. Introduction A major challenge facing researchers investigating the relationship between physiology and behavior is to integrate basic biobehavioral findings to applied fields of research. In this regard, understanding the fundamental processes by which biobehavioral factors can influence human disease is critically important for delineating pathophysiological pro- cesses, as well as for the prevention, diagnosis, and treat- ment of disease. The development and evaluation of animal models of specific human disorders have played central roles in our understanding of the relationship of behavior and disease. Well-developed animals models share features with specific human disorders on several levels including, etiology, pathogenesis, symptomatology, and responsive- ness to preventative measures and therapeutic strategies. In addition, these models often provide researchers with a greater degree of control over variables (e.g., genetic, di- etary, stressors) than in human studies, and allow for more invasive investigation of physiological functions. The work described in this article was presented as part of a research symposium entitled, “Animal Models of Dis- ease,” at the Academy of Behavioral Medicine Research (ABMR) on June 7, 1998, in Cape Cod, MA. This research is representative of many of the most important animal models of disease, including models that examine the role of behavior in viral infection, cancer, coronary heart dis- ease, cardiac arrhythmias, cardiomyopathy, and gastric ul- cer. It is anticipated that information gained from the use of these animal models will contribute to our understanding of the basic physiological and behavioral factors, as well as the clinical treatment, of human disease. 2. Stress, neuroendocrine responses, and susceptibility to infectious disease The basic premise of this work is that interacting physio- logical systems constrain a host’s resistance to challenge. Bidirectional communication among the nervous, endo- crine, and immune systems is accomplished through the shared use of ligands and receptors. Proinflammatory medi- ators (such as cytokines) released during an inflammatory response affect behavior through activation of central ner- vous system circuits. Similarly, activation of the hypotha- lamic–pituitary–adrenal axis and the sympathetic nervous system in response to a stressor, results in the release of hor- mones, neuropeptides, and neurotransmitters with immuno- modulating activity that can affect host resistance [1]. The goal of this work is to understand how the bidirectional communication among these physiological systems affect the pathogenesis of an infectious disease. In an experimental viral infection model (influenza pneu- monitis), restraint stress (RST) has been shown to cause sig- nificant suppression of both innate and adaptive immunity. As a consequence, viral pathogenesis and disease patho- physiology are altered, but the animal can terminate virus replication and no increase in mortality is observed [2,3]. However, when social reorganization (SRO) is used as the stressor, innate and adaptive immune responses are aug- mented. There is a significant alteration in viral pathogene- sis that is accompanied by enhanced inflammatory responses in the lung. Lung consolidation occurs as a consequence of a hypercellular response that is subsequently associated with enhanced mortality. An examination of the endocrine responses showed that both stressors activated the HPA axis with similar kinetics and magnitude. However, in the RST model, elevated plasma corticosterone was associated with diminished cell trafficking (reduced lymphadenopathy and cellularity in the lung), diminished NK cell activity, suppressed T cell cyto- * Corresponding author. D.B. Natelson (127B), VA Medical Center, E. Orange NJ 07018-1095.