The effect of atypical antipsychotics on the immediate-early gene, are (activity-regulated cytoskeleton-associated gene), expression was investigated in phencyclidine (PCP)-treated rats using RT-PCR. Administration of PCP (10 mg/kg) increased are mRNA levels in the prefrontal cortex, nucleus accumbens and posterior cingulate cortex. Pretreatment with clozapine (20 mg/kg), olanzapine (10 mg/kg) and risperidone (2 mg/kg), but not haloperidol (2 mg/kg), prevented PCP-induced are expression in the prefrontal cortex and nucleus accumbens. Pretreatment of haloperidol increased the striatal are mRNA levels. Clozapine, olanzapine and haloperidol inhibited the PCP-induced are expression in the posterior cingulate cortex. These results suggest that the effects of antipsychotic drugs on PCP-induced are expression in the prefrontal cortex and nucleus accumbens are useful for distinguishing atypical antipsychotic properties of the drugs. NeuroReport 11:551-555 (C) 2000 Lippincott Williams & Wilkins.