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学科主题: 基础医学
题名:
Decreased amphetamine-induced locomotion and improved latent inhibition in mice mutant for the M5 muscarinic receptor gene found in the human 15q schizophrenia region
作者: Wang, HR; Ng, K; Hayes, D; Gao, XR; Forster, G; Blaha, C; Yeomans, J
关键词: cholinergic ; mesopontine ; nucleus accumbens ; dopamine ; mesolimbic ; linkage
刊名: NEUROPSYCHOPHARMACOLOGY
发表日期: 2004-12-01
DOI: 10.1038/sj.npp.1300502
卷: 29, 期:12, 页:2126-2139
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
研究领域[WOS]: Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
关键词[WOS]: VENTRAL TEGMENTAL AREA ; KNOCK-OUT MICE ; ACETYLCHOLINE-RECEPTOR ; NUCLEUS-ACCUMBENS ; DOPAMINE EFFLUX ; GLUTAMATE RECEPTORS ; PREPULSE INHIBITION ; MURINE HEPATOCYTES ; BRAIN-STIMULATION ; SUBSTANTIA-NIGRA
英文摘要:

M5 muscarinic receptors are coexpressed with D2 dopamine receptors in the ventral tegmentum and striatum, and are important for reward in rodents. Previously, we reported that disruption of the M5 receptor gene in mice reduced dopamine release in the nucleus accumbens. In this study, we established a polymerase chain reaction (PCR) genotyping method for M5 mutant mice, and, using RT-PCR, found that M5 mRNA expression was highest in the ventral tegmentum, striatum, and thalamus in wild-type mice. In the M5 mutant mice, D2 mRNA expression was increased in several brain structures, including the striatum. Genome mapping studies showed the M5 gene is localized to chromosome 2E4 in mice, and to 15q13 in humans in the region that has been linked to schizophrenia. Amphetamine-induced locomotion, but not baseline locomotion or motor functions, decreased in M5 mutant mice, consistent with lower accumbal dopamine release. Previous reports found latent inhibition improvement in rats following nucleus accumbens lesions, or blockade of dopamine D2 receptors with neuroleptic drugs. Here, latent inhibition was significantly increased in M5 mutant mice as compared with controls, consistent with reduced dopamine function in the nucleus accumbens. In summary, our results showed that M5 gene disruption in mice decreased amphetamine-induced locomotion and increased latent inhibition, suggesting that increased M5 mesolimbic function may be relevant to schizophrenia.

语种: 英语
WOS记录号: WOS:000225302000002
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53600
Appears in Collections:基础医学院_神经生物学系_期刊论文

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作者单位: 1.Univ Toronto, Dept Psychol, Toronto, ON M5S 3G3, Canada
2.Univ S Dakota, Dept Biol, Vermillion, SD 57069 USA
3.Univ S Dakota, Neurosci Grp, Vermillion, SD 57069 USA
4.Univ Memphis, Dept Psychol, Memphis, TN 38152 USA
5.Peking Univ, Hlth Sci Ctr, Dept Neurobiol, Beijing 100871, Peoples R China
6.Tottori Univ, Fac Med, Dept Biomed Sci, Yonago, Tottori 683, Japan

Recommended Citation:
Wang, HR,Ng, K,Hayes, D,et al. Decreased amphetamine-induced locomotion and improved latent inhibition in mice mutant for the M5 muscarinic receptor gene found in the human 15q schizophrenia region[J]. NEUROPSYCHOPHARMACOLOGY,2004,29(12):2126-2139.
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