Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia

Rationale: Impaired ability to shift perceptual attentional set forms a core feature of schizophrenic illness and is associated with prefrontal cortical dysfunction. A pharmacological model producing equivalent deficits in rodents may enable the development of novel therapeutic strategies for effective treatment of cognitive impairments in schizophrenia. Objective: This study was designed to investigate the effects of phencyclidine (PCP) administration on performance in a rodent attentional set-shifting task and the neural correlates of PCP-induced deficits in task performance. Methods: Twenty-four hours following acute administration of 2.58 mg/kg PCP or vehicle, rats were tested on a perceptual attentional set shifting task (Birrell and Brown in J Neurosci 20:4320-4324, 2000). Following completion of the task, in situ hybridisation was employed to detect concurrent regional alterations in zif-268 and parvalbumin mRNA expression. Results: PCP administration selectively decreased the ability of rats to shift attentional set between perceptual dimensions (extra-dimensional shift, EDS). This impairment was accompanied by, and correlated with, decreases in expression of zif-286 in the infralimbic cortex and of parvalbumin in the dorsal reticular nucleus of the thalamus. Conclusion: 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.