Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice

Takenao Koseki, Akihiro Mouri, Takayoshi Mamiya, Yuki Aoyama, Kazuya Toriumi, Shizuka Suzuki, Azusa Nakajima, Takuma Yamada, Taku Nagai, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

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 Lys9 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 Lys9 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.

Original languageEnglish
Pages (from-to)1489-1501
Number of pages13
JournalInternational Journal of Neuropsychopharmacology
Volume15
Issue number10
DOIs
Publication statusPublished - 01-11-2012
Externally publishedYes

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Phencyclidine
Histones
Schizophrenia
Prefrontal Cortex
Histone Code
Endophenotypes
Therapeutics
Inbred ICR Mouse
Histone Deacetylase Inhibitors
Histone Deacetylases
Butyric Acid
Social Behavior
Interpersonal Relations
Pathology

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology
  • Psychiatry and Mental health

Cite this

Koseki, Takenao ; Mouri, Akihiro ; Mamiya, Takayoshi ; Aoyama, Yuki ; Toriumi, Kazuya ; Suzuki, Shizuka ; Nakajima, Azusa ; Yamada, Takuma ; Nagai, Taku ; Nabeshima, Toshitaka. / Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. In: International Journal of Neuropsychopharmacology. 2012 ; Vol. 15, No. 10. pp. 1489-1501.
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Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. / Koseki, Takenao; Mouri, Akihiro; Mamiya, Takayoshi; Aoyama, Yuki; Toriumi, Kazuya; Suzuki, Shizuka; Nakajima, Azusa; Yamada, Takuma; Nagai, Taku; Nabeshima, Toshitaka.

In: International Journal of Neuropsychopharmacology, Vol. 15, No. 10, 01.11.2012, p. 1489-1501.

Research output: Contribution to journalArticle

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