Concluding Remarks
The Brigman et al. data raise some interesting questions for further studies examining the effects of subchronic PCP on reversal in the touchscreen system. For example, would increasing the difficulty of the reversal (e.g., by increasing the perceptual similarity of the visual stimuli), presenting distracters, or making reinforcement probabilistic, increase the sensitivity of the assay to PCP treatment? Such task-dependent effects would be intriguing, given the aforementioned clinical data hinting that the range of executive deficits may increase in tandem with disease chronicity and severity. In this context, another interesting course would be to parametrically vary dose and/or chronicity of treatment to ask whether more “intensive” treatment regimens produced significant reversal deficits. Beyond the subchronic PCP model, the touchscreen-based system has great potential for evaluating mouse models of schizophrenia and, indeed, for other neuropsychiatric disorders characterized by cognitive inflexibility and other executive dysfunctions, such as depression (Holmes and Wellman, 2009) and drug addiction (Schoenbaum and Shaham, 2008). In concert with more established assays described above, the system could provide a valuable behavioral platform for elucidating the aberrant neural, molecular and genetic mechanisms underlying cognitive inflexibility in these disorders.