Behavioral animal models to assess pro-cognitive treatments for schizophrenia

Cognitive dysfunction is a core aspect of schizophrenia that constitutes a major obstacle toward reintegration of patients into society. Although multiple cognitive deficits are evident in schizophrenia patients, no medication is currently approved for their amelioration. Although consensus clinical test batteries have been developed for the assessment of putative cognition enhancers in patients with schizophrenia, parallel animal tests remain to be validated. Having no approved treatment for cognitive symptoms means no positive control can be used to examine pharmacological predictive validity of animal models. Thus, focus has been placed on animal paradigms that have demonstrable construct validity for the cognitive domain being assessed.This review describes the growing arsenal of animal paradigms under development that have putative construct validity to cognitive domains affected in schizophrenia. We discuss (1) the construct validity of the paradigms; (2) compounds developed to investigate putative treatment targets; and (3) manipulations used to first impair task performance. Focus is placed on the paradigm design, including how the use of multivariate assessments can provide evidence that main effects of treatment are not confounded by extraneous effects.