Decreased amphetamine-induced locomotion and improved latent inhibition in mice mutant for the M5 muscarinic receptor gene found in the human 15q schizophrenia region.
Decreased amphetamine-induced locomotion and improved latent inhibition in mice mutant for the M5 muscarinic receptor gene found in the human 15q schizophrenia region.
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在人类 15q 精神分裂症区域发现的 M5 毒蕈碱受体基因突变小鼠中，安非他明诱导的运动减少并改善潜在抑制。
DOI：
10.1038/sj.npp.1300502
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Yeomans,John
中科院分区：
文献类型：
--
作者：
Wang,Haoran;Ng,Karen;Hayes,David;Gao,Xiangrong;Forster,Gina;Blaha,Charles;Yeomans,John
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.
