The Attentional Set-Shifting Test Paradigm in Rats for the Screening of Novel Pro-Cognitive Compounds with Relevance for Cognitive Deficits in Schizophrenia

Cognition deficits in schizophrenia remain an untreated area, and one in which R&D investment by pharmaceutical companies is high. However, whilst many preclinical assays demonstrate pro-cognitive activity with new drugs, in the main, they have not yet been translated successfully to the clinic. In an attempt to address this and reduce the high attrition rate for drugs in the clinic, selected preclinical researchers are re-focusing their efforts on the development and validation of more translational assays. The attentional set-shifting task is an example of such an assay, which has been back-translated from the clinic to a preclinical setting. Here we review its application in schizophrenia research across humans and animals, specifically with regards to the neural basis underlying cognitive performance, the various disease-like or symptom models employed in rodents to mimic cognitive dysfunction in schizophrenia, and the resulting impact of drug treatment on executive function. Using the attentional set-shifting task, we highlight the potential promise a more translational approach can bring, whilst demonstrating the need for closer alignment in the validation and integration of this task to fully realize this promise.