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Interdisciplinary Perspectives on Infectious Diseases
Volume 2010 (2010), Article ID 380456, 10 pages
Review Article

Animal Models of Virus-Induced Neurobehavioral Sequelae: Recent Advances, Methodological Issues, and Future Prospects

Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089, USA

Received 15 August 2009; Revised 14 November 2009; Accepted 9 March 2010

Academic Editor: Marylou V. Solbrig

Copyright © 2010 Marco Bortolato and Sean C. Godar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Converging lines of clinical and epidemiological evidence suggest that viral infections in early developmental stages may be a causal factor in neuropsychiatric disorders such as schizophrenia, bipolar disorder, and autism-spectrum disorders. This etiological link, however, remains controversial in view of the lack of consistent and reproducible associations between viruses and mental illness. Animal models of virus-induced neurobehavioral disturbances afford powerful tools to test etiological hypotheses and explore pathophysiological mechanisms. Prenatal or neonatal inoculations of neurotropic agents (such as herpes-, influenza-, and retroviruses) in rodents result in a broad spectrum of long-term alterations reminiscent of psychiatric abnormalities. Nevertheless, the complexity of these sequelae often poses methodological and interpretational challenges and thwarts their characterization. The recent conceptual advancements in psychiatric nosology and behavioral science may help determine new heuristic criteria to enhance the translational value of these models. A particularly critical issue is the identification of intermediate phenotypes, defined as quantifiable factors representing single neurochemical, neuropsychological, or neuroanatomical aspects of a diagnostic category. In this paper, we examine how the employment of these novel concepts may lead to new methodological refinements in the study of virus-induced neurobehavioral sequelae through animal models.