INTERACTIONS BETWEEN SIGMA AND NMDA RECEPTORS

Sigma 和 NMDA 受体之间的相互作用

• 批准号: 2430883
• 负责人: J. Michael Walker
• 金额: $ 9.96万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430883
• 关键词: NMDA receptors; PCP receptor; dopamine; dopamine antagonists; electrophysiology; excitatory aminoacid; glycine; hippocampus; inhibitor /antagonist; laboratory rat; long term potentiation; molecular site; neuropharmacology; polyamines; receptor binding; reticular formation; substantia nigra; zinc

Recent work has demonstrated that very low doses (1 mug/kg, i.v.) can approximately double the excitatory effect of NMDA iontophoretically applied to hippocampal (CA3) pyramidal neurons. Furthermore, the NMDA antagonist CPP was found to inhibit the increased glucose utilization produced by the sigma ligand DTG (1 mg/kg, i.p.), and CPP blocks the ability of DTG to cause increased dopamine release. Based on these findings it appears that sigma ligands (at least in some cases) positively modulate NMDA responses. Three sets of experiments are proposed to further examine this possibility in order to 1) Further characterize the interactions between sigma and NMDA in the hippocampus; 2) use the radioligand binding techniques to examine whether such interactions can be observed at the level of membrane-receptor interactions; and 3) to determine the generality of these interactions - i.e., to examine whether sigma/NMDA interactions are found in neural systems outside the hippocampus, with special emphasis on the nigrostriatal dopamine system. These experiments are relevant to mental health. Some experiments suggest that sigma ligands may serve as antipsychotic drugs, or as pharmacotherapeutic agents for antipsychotic drug-induced movement disorders. In addition, the investigations in the hippocampus may have relevance to learning and memory and thus have implications for certain mental illnesses such as Alzheimer's disease or other diseases that affect mental health.

最近的研究表明，非常低的剂量（1微克/公斤，静脉注射），可以 大约两倍的兴奋作用的NMDA离子电渗 应用于海马（CA 3）锥体神经元。 此外，NMDA 拮抗剂CPP可抑制葡萄糖利用的增加 通过σ配体DTG（1 mg/kg，i. p.）产生，而CPP阻止了 DTG引起多巴胺释放增加的能力 基于这些 研究发现，似乎sigma配体（至少在某些情况下） 正调节NMDA反应。 三组实验是 建议进一步研究这一可能性，以便：（1）进一步 表征海马中sigma和NMDA之间的相互作用; 2)使用放射性配体结合技术来检查这种 可以在膜受体水平上观察到相互作用 3）确定这些相互作用的一般性- 也就是说，为了研究sigma/NMDA相互作用是否在神经元中被发现， 海马体外的系统，特别强调 黑质纹状体多巴胺系统 这些实验与心理健康有关。 一些实验 这表明σ配体可以作为抗精神病药物，或作为 用于抗精神病药物引起的运动的药物制剂 紊乱 此外，海马区的调查可能 与学习和记忆的相关性，因此对某些 精神疾病，如阿尔茨海默病或其他疾病， 影响心理健康。

项目成果

Local effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus.

• DOI: 10.1016/s0014-2999(98)00374-4
• 发表时间: 1998-07
• 期刊: European journal of pharmacology
• 影响因子: 5
• 作者: Adrienne S. Miller;J. Michael Walker

Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat.

丘脑底核在大鼠黑质大麻素作用中的作用。

• DOI: 10.1152/jn.1997.77.3.1635
• 发表时间: 1997
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Sañudo-Peña,MC;Walker,JM
• 通讯作者: Walker,JM

Dopaminergic system does not play a major role in the precipitated cannabinoid withdrawal syndrome.

多巴胺能系统在促发大麻素戒断综合征中不起主要作用。

• 发表时间: 1999
• 期刊: Zhongguo yao li xue bao = Acta pharmacologica Sinica.
• 作者: Sanudo-Pena,MC;Force,M;Tsou,K;McLemore,G;Roberts,L;Walker,JM
• 通讯作者: Walker,JM

A novel neurotransmitter system involved in the control of motor behavior by the basal ganglia.

一种新型神经递质系统，参与基底神经节控制运动行为。

• DOI: 10.1111/j.1749-6632.1998.tb09081.x
• 发表时间: 1998
• 期刊: Annals of the New York Academy of Sciences
• 影响因子: 5.2
• 作者: Sañudo-Peña,MC;Walker,JM
• 通讯作者: Walker,JM

Fatty acid amide hydrolase is located preferentially in large neurons in the rat central nervous system as revealed by immunohistochemistry.

免疫组织化学显示，脂肪酸酰胺水解酶优先位于大鼠中枢神经系统的大神经元中。

• DOI: 10.1016/s0304-3940(98)00700-9
• 发表时间: 1998
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Tsou,K;Nogueron,MI;Muthian,S;Sañudo-Pena,MC;Hillard,CJ;Deutsch,DG;Walker,JM
• 通讯作者: Walker,JM