Essential role of NMDA receptor channel ε4 subunit (GluN2D) in the effects of phencyclidine, but not methamphetamine.
Essential role of NMDA receptor channel ε4 subunit (GluN2D) in the effects of phencyclidine, but not methamphetamine.
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DOI：
10.1371/journal.pone.0013722
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发表时间：
2010-10-28
期刊：
影响因子：
3.7
通讯作者：
Ikeda K
中科院分区：
文献类型：
--
作者：
Hagino Y;Kasai S;Han W;Yamamoto H;Nabeshima T;Mishina M;Ikeda K
苯环利定（PCP）是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，可增加啮齿动物的运动活动，并引起人类精神分裂症样症状。虽然多巴胺（DA）通路的激活被假设为介导PCP的这些作用，但PCP诱导其作用的确切机制仍有待阐明。本研究采用体内微透析技术，在缺乏NMDA受体通道ε1或ε4亚基（GluRε1 [GluN 2A]或GluRε4 [GluN 2D]）和运动活性的小鼠中，研究PCP对纹状体和前额叶皮质（PFC）细胞外DA（DAex）水平的影响。PCP显著增加野生型和GluRε1敲除小鼠纹状体和PFC中的DAex，但不增加GluR ε 4敲除小鼠纹状体和PFC中的DAex。目前的结果表明，PCP增强多巴胺能传递，并通过作用于GluRε4增加自发活动。
Phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, increases locomotor activity in rodents and causes schizophrenia-like symptoms in humans. Although activation of the dopamine (DA) pathway is hypothesized to mediate these effects of PCP, the precise mechanisms by which PCP induces its effects remain to be elucidated. The present study investigated the effect of PCP on extracellular levels of DA (DAex) in the striatum and prefrontal cortex (PFC) using in vivo microdialysis in mice lacking the NMDA receptor channel ε1 or ε4 subunit (GluRε1 [GluN2A] or GluRε4 [GluN2D]) and locomotor activity. PCP significantly increased DAex in wildtype and GluRε1 knockout mice, but not in GluRε4 knockout mice, in the striatum and PFC. Acute and repeated administration of PCP did not increase locomotor activity in GluRε4 knockout mice. The present results suggest that PCP enhances dopaminergic transmission and increases locomotor activity by acting at GluRε4.
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影响因子：
5.3
作者：
Adams, B;Moghaddam, B
通讯作者：
Moghaddam, B
影响因子：
6.1
作者：
GAREY, RE;HEATH, RG
通讯作者：
HEATH, RG
影响因子：
3.4
作者：
BENWELL, MEM;BALFOUR, DJK;LUCCHI, HM
通讯作者：
LUCCHI, HM
影响因子：
2.7
作者：
Hertel, P;Mathe, JM;Svensson, TH
通讯作者：
Svensson, TH
DOI：
10.1016/0169-328x(95)00107-4
发表时间：
1995-10-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
IKEDA, K;ARAKI, K;MISHINA, M
通讯作者：
MISHINA, M