Translationally relevant modeling of PTSD in rodents

Post-traumatic stress disorder (PTSD) is clinically defined in DSM-4 by exposure to a significantly threatening and/or horrifying event and the presence of a certain number of symptoms from each of three symptom clusters at least one month after the event. Since humans clearly do not respond homogeneously to a potentially traumatic experience, the heterogeneity in animal responses might be regarded as confirming the validity of animal studies, rather than as representing a problem. A model of diagnostic criteria for psychiatric disorders could therefore be applied to animal responses to augment the validity of study data, providing that the criteria for classification are clearly defined, reliably reproducible and yield results that conform to findings in human subjects. The method described herein was developed in an attempt to model diagnostic criteria in terms of individual patterns of response by using behavioral measures and determining cut-off scores to distinguish between extremes of response or non-response, leaving a sizeable proportion of subjects in a middle group, outside each set of cut-off criteria. The cumulative results of our studies indicate that the contribution of animal models can be further enhanced by classifying individual animal study subjects according to their response patterns. The animal model also enables the researcher to go one step further and correlate specific anatomic, bio-molecular and physiological parameters with the degree and pattern of the individual behavioral response and introduces "prevalence rates" as a parameter. The translational value of the classification method and future directions are discussed.