Comprehensive behavioral study of mGluR3 knockout mice: Implication in schizophrenia related endophenotypes

Ryuta Fujioka, Takenobu Nii, Akiko Iwaki, Atsushi Shibata, Isao Ito, Kiyoyuki Kitaichi, Masatoshi Nomura, Satoko Hattori, Keizo Takao, Tsuyoshi Miyakawa, Yasuyuki Fukumaki

研究成果: ジャーナルへの寄稿記事

27 引用 (Scopus)

抄録

Background: We previously performed systematic association studies of glutamate receptor gene family members with schizophrenia, and found positive associations of polymorphisms in the GRM3 (a gene of metabotropic glutamate receptor 3: mGluR3) with the disorder. Physiological roles of GRM3 in brain functions and its functional roles in the pathogenesis of schizophrenia remain to be resolved. Results: We generated mGluR3 knockout (KO) mice and conducted comprehensive behavioral analyses. KO mice showed hyperactivity in the open field, light/dark transition, and 24-hour home cage monitoring tests, impaired reference memory for stressful events in the Porsolt forced swim test, impaired contextual memory in cued and contextual fear conditioning test, and impaired working memory in the T-Maze forced alternation task test. Hyperactivity and impaired working memory are known as endophenotypes of schizophrenia. We examined long-term synaptic plasticity by assessing long-term potentiation (LTP) in the CA1 region in the hippocampi of KO and wild-type (WT) mice. We observed no differences in the amplitude of LTP between the two genotypes, suggesting that mGluR3 is not essential for LTP in the CA1 region of the mouse hippocampus. As hyperactivity is typically associated with increased dopaminergic transmission, we performed in vivo microdialysis measurements of extracellular dopamine in the nucleus accumbens of KO and WT mice. We observed enhancements in the methamphetamine (MAP)-induced release of dopamine in KO mice. Conclusions: These results demonstrate that a disturbance in the glutamate-dopamine interaction may be involved in the pathophysiology of schizophrenia-like behavior, such as hyperactivity in mGluR3 KO mice.

元の言語英語
記事番号31
ジャーナルMolecular Brain
7
発行部数1
DOI
出版物ステータス出版済み - 4 23 2014

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Endophenotypes
Knockout Mice
Schizophrenia
Long-Term Potentiation
Dopamine
Short-Term Memory
Hippocampus
Neuronal Plasticity
Methamphetamine
Microdialysis
Nucleus Accumbens
Glutamate Receptors
Genes
Fear
metabotropic glutamate receptor 3
Glutamic Acid
Genotype
Light
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

これを引用

Fujioka, R., Nii, T., Iwaki, A., Shibata, A., Ito, I., Kitaichi, K., ... Fukumaki, Y. (2014). Comprehensive behavioral study of mGluR3 knockout mice: Implication in schizophrenia related endophenotypes. Molecular Brain, 7(1), [31]. https://doi.org/10.1186/1756-6606-7-31

Comprehensive behavioral study of mGluR3 knockout mice : Implication in schizophrenia related endophenotypes. / Fujioka, Ryuta; Nii, Takenobu; Iwaki, Akiko; Shibata, Atsushi; Ito, Isao; Kitaichi, Kiyoyuki; Nomura, Masatoshi; Hattori, Satoko; Takao, Keizo; Miyakawa, Tsuyoshi; Fukumaki, Yasuyuki.

:: Molecular Brain, 巻 7, 番号 1, 31, 23.04.2014.

研究成果: ジャーナルへの寄稿記事

Fujioka, R, Nii, T, Iwaki, A, Shibata, A, Ito, I, Kitaichi, K, Nomura, M, Hattori, S, Takao, K, Miyakawa, T & Fukumaki, Y 2014, 'Comprehensive behavioral study of mGluR3 knockout mice: Implication in schizophrenia related endophenotypes', Molecular Brain, 巻. 7, 番号 1, 31. https://doi.org/10.1186/1756-6606-7-31
Fujioka, Ryuta ; Nii, Takenobu ; Iwaki, Akiko ; Shibata, Atsushi ; Ito, Isao ; Kitaichi, Kiyoyuki ; Nomura, Masatoshi ; Hattori, Satoko ; Takao, Keizo ; Miyakawa, Tsuyoshi ; Fukumaki, Yasuyuki. / Comprehensive behavioral study of mGluR3 knockout mice : Implication in schizophrenia related endophenotypes. :: Molecular Brain. 2014 ; 巻 7, 番号 1.
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AU - Nomura, Masatoshi

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