Acute administration of PCP produces deficits in perceptual set shifting comparable to an aspect of executive dysfunction in schizophrenia. Moreover, this impairment is associated with altered medial prefrontal cortical and reticular thalamic activity. Therefore, this rodent paradigm may model the set-shifting deficits that form a core feature of schizophrenic pathology.

The temporally distinct behavioral effects of these PCP treatment regimes suggest that PPI deficits relate directly to acute NMDA receptor antagonism, whereas the more enduring set shifting deficits relate to the longer term consequences of NMDA receptor blockade. Therefore, these subchronic and chronic PCP treatment regimes produce hypofrontality (Cochran et al., Neuropsychopharmacology, 28:265-275, 2003) and associated prefrontal cortex-dependent deficits in behavioral flexibility which mirror core deficits in schizophrenia.