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Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment.

Abstract

In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, 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 deficits 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 neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of schizophrenia, schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia.

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  • Authors+Show Affiliations

    ,

    Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan.

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    Source

    MeSH

    Animals
    Animals, Newborn
    Brain
    Disease Models, Animal
    Excitatory Amino Acid Antagonists
    Glutamic Acid
    Humans
    Phencyclidine
    Receptors, N-Methyl-D-Aspartate
    Schizophrenia
    Synaptic Transmission

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17669558

    Citation

    Mouri, Akihiro, et al. "Phencyclidine Animal Models of Schizophrenia: Approaches From Abnormality of Glutamatergic Neurotransmission and Neurodevelopment." Neurochemistry International, vol. 51, no. 2-4, 2007, pp. 173-84.
    Mouri A, Noda Y, Enomoto T, et al. Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int. 2007;51(2-4):173-84.
    Mouri, A., Noda, Y., Enomoto, T., & Nabeshima, T. (2007). Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochemistry International, 51(2-4), pp. 173-84.
    Mouri A, et al. Phencyclidine Animal Models of Schizophrenia: Approaches From Abnormality of Glutamatergic Neurotransmission and Neurodevelopment. Neurochem Int. 2007;51(2-4):173-84. PubMed PMID: 17669558.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment. AU - Mouri,Akihiro, AU - Noda,Yukihiro, AU - Enomoto,Takeshi, AU - Nabeshima,Toshitaka, Y1 - 2007/06/27/ PY - 2007/05/08/received PY - 2007/06/05/revised PY - 2007/06/07/accepted PY - 2007/8/3/pubmed PY - 2007/10/27/medline PY - 2007/8/3/entrez SP - 173 EP - 84 JF - Neurochemistry international JO - Neurochem. Int. VL - 51 IS - 2-4 N2 - In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, 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 deficits 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 neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of schizophrenia, schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/17669558/Phencyclidine_animal_models_of_schizophrenia:_approaches_from_abnormality_of_glutamatergic_neurotransmission_and_neurodevelopment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(07)00171-4 DB - PRIME DP - Unbound Medicine ER -