Phencyclidine-induced cognitive impairment and its neural mechanisms

Yukihiro Noda, Akihiro Mouri, Hirotake Hida, Toshitaka Nabeshima

研究成果: Chapter

抜粋

Cognitive dysfunction in schizophrenia remains an unmet clinical challenge. To develop novel therapeutics for cognitive dysfunction, understanding the neuro-and psychopathology of such dysfunction using the validated animal models is needed. Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis, including positive symptoms, negative symptoms and cognitive dysfunction in humans. The glutamate dysfunction hypothesis is one of the main explanatory hypotheses in schizophrenia, and animals administered PCP have been utilized for the elucidation of pathology and the evaluation of therapeutics. Adult rodents administered PCP acutely show a sensorimotor gating deficit in a prepulse inhibition test. Acute and subchronic PCP administrations induce cognitive dysfunction in several learning and memory tests, as well as positive-and negative-like behavioral abnormalities. Some cognitive behavioral changes endure after withdrawal from subchronic PCP administration. Furthermore, subchronic PCP administration induces neurochemical and neuronanatomical changes that are similar to those in schizophrenia. Also noteworthy, converging evidence from epidemiological, brain imaging and neuropathological studies suggests that schizophrenia is a developmental disorder. The NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on the neurodevelopment hypothesis of schizophrenia, a schizophrenia-like model using rodents administered PCP at the perinatal stage has been developed. Perinatal PCP administration impairs neuronal development and induces long-lasting cognitive dysfunction in the adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming the pathological mechanisms of cognitive dysfunction in schizophrenia.

元の言語English
ホスト出版物のタイトルAdvances in Cognitive and Behavioral Sciences
出版者Nova Science Publishers, Inc.
ページ237-274
ページ数38
ISBN(電子版)9781629488936
ISBN(印刷物)9781629488905
出版物ステータスPublished - 01-01-2014
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Psychology(all)
  • Medicine(all)

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    Noda, Y., Mouri, A., Hida, H., & Nabeshima, T. (2014). Phencyclidine-induced cognitive impairment and its neural mechanisms. : Advances in Cognitive and Behavioral Sciences (pp. 237-274). Nova Science Publishers, Inc..