期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 15, 期 10, 页码 1489-1501出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145711001672
关键词
Enriched environment; histone acetylation; phencyclidine; schizophrenia
资金
- Exploratory Research from the JSPS as part of the 'Academic Frontier' Project for Private Universities of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [19659017, 22659213]
- Regional Joint Research Program
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Research on Regulatory Science of Pharmaceuticals and Medical Devices from the Ministry of Health and Labour Sciences and the Ministry of Health, Labour and Welfare, Japan (MHLW)
- Research on Risk of Chemical Substances, Health and Labour Science Research Grants
- Ministry of Health, Labour and Welfare (MHLW
- Japan-Korea basic scientific cooperation program (JSPS)
- JSPS [23791325]
- [22248033]
- [20390073]
- [21390045]
- Grants-in-Aid for Scientific Research [22659213, 24590304, 23791325] Funding Source: KAKEN
Enriched environments (EEs) during development have been shown to influence adult behaviour. Environmental conditions during childhood may contribute to the onset and/or pathology of schizophrenia; however, it remains unclear whether EE might prevent the development of schizophrenia. Herein, we investigated the effects of EE during adolescence on phencyclidine (PCP)-induced abnormal behaviour, a proposed schizophrenic endophenotype. Male ICR mice (3 wk old) were exposed to an EE for 4 wk and then treated with PCP for 2 wk. The EE potentiated the acute PCP treatment-induced hyperlocomotion in the locomotor test and prevented chronic PCP treatment-induced impairments of social behaviour and recognition memory in the social interaction and novel object recognition tests. It also prevented the PCP-induced decrease of acetylated Lys(9) in histone H3-positive cells and increase of the histone deacetylase (HDAC) 5 level in the prefrontal cortex. To investigate whether the histone modification during adolescence might be critical for the effect of EE, 3-wk-old mice were first treated with sodium butyrate (SB; an HDAC inhibitor) for 4 wk and then treated with PCP for 2 wk. Chronic SB treatment during adolescence mimicked the effects of EE, including potentiation of hyperlocomotion induced by acute PCP treatment and prevention of social and cognitive impairments, decrease of acetylated Lys(9) in histone H3-positive cells and increase of the HDAC5 level in the prefrontal cortex associated with chronic PCP treatment. Our results suggest that EEs prevent PCP-induced abnormal behaviour associated with histone deacetylation. EEs during childhood might prove to be a novel strategy for prophylaxis against schizophrenia.
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