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The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia.
Neuropsychopharmacology 1999; 20(3):201-25N

Abstract

Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology, findings that have contributed to a hypoglutamatergic hypothesis of schizophrenia. Moreover, a history of experimental investigations of the effects of these drugs in animals suggests that NMDA receptor antagonists may model some behavioral symptoms of schizophrenia in nonhuman subjects. In this review, the usefulness of PCP administration as a potential animal model of schizophrenia is considered. To support the contention that NMDA receptor antagonist administration represents a viable model of schizophrenia, the behavioral and neurobiological effects of these drugs are discussed, especially with regard to differing profiles following single-dose and long-term exposure. The neurochemical effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Future directions for the application of NMDA receptor antagonist models of schizophrenia to preclinical and pathophysiological research are offered.

Authors+Show Affiliations

Neuropsychopharmacology Research Unit, Yale University School of Medicine, New Haven, Connecticut 06520-8001, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

10063482

Citation

Jentsch, J D., and R H. Roth. "The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 20, no. 3, 1999, pp. 201-25.
Jentsch JD, Roth RH. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology. 1999;20(3):201-25.
Jentsch, J. D., & Roth, R. H. (1999). The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 20(3), pp. 201-25.
Jentsch JD, Roth RH. The Neuropsychopharmacology of Phencyclidine: From NMDA Receptor Hypofunction to the Dopamine Hypothesis of Schizophrenia. Neuropsychopharmacology. 1999;20(3):201-25. PubMed PMID: 10063482.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. AU - Jentsch,J D, AU - Roth,R H, PY - 1999/3/4/pubmed PY - 1999/3/4/medline PY - 1999/3/4/entrez SP - 201 EP - 25 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 20 IS - 3 N2 - Administration of noncompetitive NMDA/glutamate receptor antagonists, such as phencyclidine (PCP) and ketamine, to humans induces a broad range of schizophrenic-like symptomatology, findings that have contributed to a hypoglutamatergic hypothesis of schizophrenia. Moreover, a history of experimental investigations of the effects of these drugs in animals suggests that NMDA receptor antagonists may model some behavioral symptoms of schizophrenia in nonhuman subjects. In this review, the usefulness of PCP administration as a potential animal model of schizophrenia is considered. To support the contention that NMDA receptor antagonist administration represents a viable model of schizophrenia, the behavioral and neurobiological effects of these drugs are discussed, especially with regard to differing profiles following single-dose and long-term exposure. The neurochemical effects of NMDA receptor antagonist administration are argued to support a neurobiological hypothesis of schizophrenia, which includes pathophysiology within several neurotransmitter systems, manifested in behavioral pathology. Future directions for the application of NMDA receptor antagonist models of schizophrenia to preclinical and pathophysiological research are offered. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/10063482/The_neuropsychopharmacology_of_phencyclidine:_from_NMDA_receptor_hypofunction_to_the_dopamine_hypothesis_of_schizophrenia_ L2 - http://dx.doi.org/10.1016/S0893-133X(98)00060-8 DB - PRIME DP - Unbound Medicine ER -