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Phencyclidine and genetic animal models of schizophrenia developed in relation to the glutamate hypothesis.
Methods Find Exp Clin Pharmacol 2007; 29(4):291-301MF

Abstract

In humans, phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, PCP-treated animals have been utilized as an animal model of schizophrenia. PCP-treated animals exhibit hyperlocomotion as an index of positive symptoms, and a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficit and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuronanatomical changes. Recently, genetic approaches based on "the glutamate hypothesis of schizophrenia" have been used to develop animal models of schizophrenia. NMDA receptor subunit zeta1 knockdown, epsilon1 knockout (KO) and zeta1 point mutant mice exhibiting a hypofunction of NMDA receptors show hyperlocomotion, social behavioral deficit, sensorimotor gating deficit or cognitive dysfunction. Forebrain-specific calcineurin KO, neuregulin 1 heterozygous KO and lysophosphatidic acid 1 receptor KO mice can also serve as animal models of schizophrenia. These findings suggest that PCP and genetic animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia.

Authors+Show Affiliations

Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

17609743

Citation

Enomoto, T, et al. "Phencyclidine and Genetic Animal Models of Schizophrenia Developed in Relation to the Glutamate Hypothesis." Methods and Findings in Experimental and Clinical Pharmacology, vol. 29, no. 4, 2007, pp. 291-301.
Enomoto T, Noda Y, Nabeshima T. Phencyclidine and genetic animal models of schizophrenia developed in relation to the glutamate hypothesis. Methods Find Exp Clin Pharmacol. 2007;29(4):291-301.
Enomoto, T., Noda, Y., & Nabeshima, T. (2007). Phencyclidine and genetic animal models of schizophrenia developed in relation to the glutamate hypothesis. Methods and Findings in Experimental and Clinical Pharmacology, 29(4), pp. 291-301.
Enomoto T, Noda Y, Nabeshima T. Phencyclidine and Genetic Animal Models of Schizophrenia Developed in Relation to the Glutamate Hypothesis. Methods Find Exp Clin Pharmacol. 2007;29(4):291-301. PubMed PMID: 17609743.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phencyclidine and genetic animal models of schizophrenia developed in relation to the glutamate hypothesis. AU - Enomoto,T, AU - Noda,Y, AU - Nabeshima,T, PY - 2007/7/5/pubmed PY - 2007/10/5/medline PY - 2007/7/5/entrez SP - 291 EP - 301 JF - Methods and findings in experimental and clinical pharmacology JO - Methods Find Exp Clin Pharmacol VL - 29 IS - 4 N2 - In humans, phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, PCP-treated animals have been utilized as an animal model of schizophrenia. PCP-treated animals exhibit hyperlocomotion as an index of positive symptoms, and a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficit and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuronanatomical changes. Recently, genetic approaches based on "the glutamate hypothesis of schizophrenia" have been used to develop animal models of schizophrenia. NMDA receptor subunit zeta1 knockdown, epsilon1 knockout (KO) and zeta1 point mutant mice exhibiting a hypofunction of NMDA receptors show hyperlocomotion, social behavioral deficit, sensorimotor gating deficit or cognitive dysfunction. Forebrain-specific calcineurin KO, neuregulin 1 heterozygous KO and lysophosphatidic acid 1 receptor KO mice can also serve as animal models of schizophrenia. These findings suggest that PCP and genetic animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia. SN - 0379-0355 UR - https://www.unboundmedicine.com/medline/citation/17609743/Phencyclidine_and_genetic_animal_models_of_schizophrenia_developed_in_relation_to_the_glutamate_hypothesis_ L2 - http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summaryn_pr?p_JournalId=6&p_RefId=1075358 DB - PRIME DP - Unbound Medicine ER -