Continuous Phencyclidine Treatment Induces Schizophrenia-Like Hyperreactivity of Striatal Dopamine Release

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 25; no. 2; pp. 157 - 164
• Main Authors: Balla, Andrea, Koneru, Rajeth, Smiley, John, Sershen, Henry, Javitt, Daniel C
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2001; Nature Publishing; Nature Publishing Group
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Adult and adolescent clinical studies; Amphetamine; Amphetamine - pharmacology; Amphetamines; Animals; Biological and medical sciences; Central Nervous System Stimulants - pharmacology; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine; Dopamine - biosynthesis; Excitatory Amino Acid Antagonists - pharmacology; Glutamate; Homovanillic Acid - metabolism; Hyperactivity; Ketamine; Male; Medical sciences; Motor Activity - drug effects; Motor Activity - physiology; NMDA receptors; Phencyclidine - administration & dosage; Phencyclidine - pharmacology; Psychiatric research; Psychology. Psychoanalysis. Psychiatry; Psychomotor Agitation - metabolism; Psychopathology. Psychiatry; Psychoses; Psychosis; Rats; Rats, Sprague-Dawley; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - metabolism; Striatum; New York; United States > US; Striatum; Amphetamine; Dopamine; NMDA receptors; Glutamate; Amphetamine derivatives; Animal model; Rat; Metabolite; Pathogenesis; Psychotropic; Toxicity; Central nervous system; Schizophrenia; Glutamate receptor; Psychosis; Phencyclidine; Piperidine derivatives; Amfetamine; Subcutaneous administration; Antagonist; Nervous system diseases; CNS stimulant; Rodentia; Corpus striatum; Catecholamine; Long term; Cerebral disorder; Locomotion; Vertebrata; Mammalia; Animal; Central nervous system disease; NMDA receptor; Brain (vertebrata)
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1016/S0893-133X(01)00230-5

Functional dopaminergic hyperactivity is a key feature of schizophrenia. Recent in vivo imaging studies have demonstrated greater striatal dopamine release in response to amphetamine challenge in schizophrenia subjects than in normal controls. N-methyl-d-aspartate (NMDA) receptors are known to play a prominent role in regulation of striatal dopamine release. In humans, NMDA antagonists induce a psychotic state that closely resembles schizophrenia. The present study investigates the degree to which chronic continuous administration of the NMDA antagonist phencyclidine (PCP) induces schizophrenia-like hyperreactivity of striatal dopamine release to amphetamine in rodents. Rats were treated with 10 or 15 mg/kg/d PCP for two weeks by osmotic minipump, and striatal dopamine release to amphetamine challenge (1 mg/kg) was monitored by microdialysis. PCP-treated rats showed significant enhancement in amphetamine-induced dopamine release, along with significantly enhanced locomotor activity. These findings support the concept that NMDA receptor dysfunction may contribute to dopaminergic dysfunction in schizophrenia.