Continuous phencyclidine treatment induces schizophrenia-like hyperreactivity of striatal dopamine release

Functional dopaminergic hyperactivity is a key feature of schizophrenia. Re cent in vivo imaging studies have demonstrated greater striatal dopamine re lease in response to amphetamine challenge in schizophrenia subjects than i n normal controls. N-methyl-D-aspartate (NMDA) receptors are known to play a prominent role in regulation of striatal dopamine release, In humans, NMD A antagonists induce a psychotic state that closely resembles schizophrenia . The present study investigates the degree to which chronic continuous adm inistration of the NMDA antagonist phencyclidine (PCP) induces schizophreni a-like hyperreactivity of striatal dopamine release to amphetamine in roden ts, Rats were treated with 10 or 15 mg/kg/d PCP for two weeks by osmotic mi nipump, and striatal dopamine release to amphetamine challenge (1 mg/kg) wa s monitored by microdialysis. PCP-treated rats showed significant enhanceme nt in amphetamine-induced dopamine release, along with significantly enhanc ed locomotor activity. These findings support the concept that NMDA recepto r dysfunction may contribute to dopaminergic dysfunction in schizophrenia. [Neuropsychopharmacology 25:157-164,2001] (C) 2001 American College of Neur opsychopharmacology. Published by Elsevier Science Inc.