Neuropsychopharmacological study on an animal model for negative symptom of schizophrenia induced by repeated phencyclidine treatment

Y. Noda, T. Nabeshima

研究成果: Review article

8 引用 (Scopus)

抄録

To develop an animal model for negative symptoms, in particular avolition, of schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as avolition) in the forced swimming test was investigated in mice, since PCP produces negative symptoms in humans. Unlike single, repeated treatment with PCP prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment. The enhancing effect of PCP on the immobility persisted for 21 d after the withdrawal of the drug. Atypical antipsychotics attenuated the enhancing effect of PCP on the immobility. Since these attenuating effects were antagonized by a serotonin-S2 receptor agonist, (±)-2,5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via serotonin-S2 receptors. In contrast with atypical antipsychotics, typical antipsychotics, antidepressants and anxiolytics had no effect. No functional changes in post-synaptic serotonin-S2 receptors were observed in PCP-treated mice following the forced swimming test. Serotonin utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in PCP-treated mice showing the enhancement of immobility. The enhancing effect of PCP was significantly attenuated by D-cycloserine, an agonist for glycine binding site of N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA receptor function or of the cortical glutamate and glycine levels were observed in PCP-treated mice showing the enhancement of immobility. These results suggest that the enhancing effect of PCP on immobility is mediated by the imbalance of the cortical serotonergic, dopaminergic and glutamatergic systems and could be used as an animal model for negative symptoms of schizophrenia.

元の言語English
ページ(範囲)677-682
ページ数6
ジャーナルYakugaku Zasshi
120
発行部数8
DOI
出版物ステータスPublished - 01-01-2000

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Phencyclidine
Serotonin 5-HT2 Receptors
Schizophrenia
Animal Models
Antipsychotic Agents
N-Methyl-D-Aspartate Receptors
Glycine
Cycloserine
Serotonin Receptor Agonists
Ionophores
Anti-Anxiety Agents
Therapeutics
Prefrontal Cortex
Antidepressive Agents
Glutamic Acid
Dopamine
Serotonin
Binding Sites
Injections
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

これを引用

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abstract = "To develop an animal model for negative symptoms, in particular avolition, of schizophrenia, the effect of phencyclidine (PCP) on immobility (regarded as avolition) in the forced swimming test was investigated in mice, since PCP produces negative symptoms in humans. Unlike single, repeated treatment with PCP prolonged the immobility time in the forced swimming test 24 h after the final injection compared with saline treatment. The enhancing effect of PCP on the immobility persisted for 21 d after the withdrawal of the drug. Atypical antipsychotics attenuated the enhancing effect of PCP on the immobility. Since these attenuating effects were antagonized by a serotonin-S2 receptor agonist, (±)-2,5-dimethoxy-4-iodamphetamine (DOI), the effects may be mediated via serotonin-S2 receptors. In contrast with atypical antipsychotics, typical antipsychotics, antidepressants and anxiolytics had no effect. No functional changes in post-synaptic serotonin-S2 receptors were observed in PCP-treated mice following the forced swimming test. Serotonin utilization in the prefrontal cortex was increased, but dopamine utilization was decreased in PCP-treated mice showing the enhancement of immobility. The enhancing effect of PCP was significantly attenuated by D-cycloserine, an agonist for glycine binding site of N-methyl-D-aspartate (NMDA) receptor ionophore complex. Decreases of NMDA receptor function or of the cortical glutamate and glycine levels were observed in PCP-treated mice showing the enhancement of immobility. These results suggest that the enhancing effect of PCP on immobility is mediated by the imbalance of the cortical serotonergic, dopaminergic and glutamatergic systems and could be used as an animal model for negative symptoms of schizophrenia.",
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