Theoretical and practical considerations behind the use of laboratory animals for the study of Tourette syndrome.

In the present manuscript we review a substantial body of literature describing several pre-clinical animal models designed and developed with the purpose of investigating the biological determinants of Tourette syndrome (TS). In order to map the animal models onto the theoretical background upon which they have been devised, we first define phenomenological and etiological aspects of TS and then match this information to the available pre-clinical models. Thus, we first describe the characteristic symptoms exhibited by TS patients and then a series of hypotheses attempting to identify the multifactorial causes of TS. With respect to the former, we detail the phenomenology of abnormal repetitive behaviors (tics and stereotypies), obsessive-compulsive behaviors and aberrant sensory-motor gating. With respect to the latter, we describe both potential candidate vulnerability genes and environmental factors (difficult pregnancies, psychosocial stressors and infections). We then discuss how this evidence has been translated in pre-clinical research with respect to both dependent (symptoms) and independent (etiological factors) variables. Thus, while, on the one hand, we detail the methodologies adopted to measure abnormal repetitive and obsessive-compulsive behaviors, and sensory-motor gating, on the other hand, we describe genetic engineering studies and environmental modulations aimed at reproducing the proposed biological determinants in laboratory rodents. A special emphasis is placed upon "programming" events, occurring during critical stages of early development and exerting organizational delayed consequences. In the final section, we outline a heuristic model with the purpose of integrating clinical and pre-clinical evidence in the study of TS.
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