RATIONALE: Selective cognitive impairments, including those of executive 
function as assessed using the Wisconsin Card Sort Test or 
intradimensional-extradimensional (ID-ED) tests, are a key feature of 
schizophrenia but remain inadequately treated by existing therapies. Recently, 
however, modafinil has been shown to improve attentional set-shifting 
performance in patients with schizophrenia.
OBJECTIVE: The present study evaluated the recently described analogous rat 
ID-ED attentional set-shifting task by investigating the effects of various 
pharmacological challenges to a phencyclidine (PCP)-induced ED shift impairment, 
namely, haloperidol, risperidone, sertindole, and modafinil.
MATERIALS AND METHODS: Rats were subjected to a subchronic systemic 
administration of either saline vehicle or PCP (5 mg/kg i.p. b.i.d. for 7 days) 
followed by a 7-day washout period. During this period, rats were trained to dig 
in baited bowls for a food reward and to discriminate based on odor or digging 
media. In a single test session conducted the day after the washout period (day 
8), rats performed a series of discriminations following acute administration of 
either vehicle, or haloperidol (0.1 mg/kg s.c.), or risperidone (0.2 mg/kg 
i.p.), or sertindole (1.25 mg/kg p.o.) or modafinil (64 mg/kg p.o.).
RESULTS: The subchronic PCP-induced ED deficit was ameliorated by sertindole and 
modafinil but not by haloperidol or risperidone.
CONCLUSIONS: Overall, these findings further support that the rat ID-ED test in 
subchronic PCP-treated rats has utility and validity as a preclinical model of 
the cognitive symptoms of schizophrenia and demonstrates back-translational 
potential.