INTERACTIONS BETWEEN SIGMA AND NMDA RECEPTORS

Sigma 和 NMDA 受体之间的相互作用

• 批准号: 3070368
• 负责人: J. Michael Walker
• 金额: $ 8.52万
• 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 1998-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3070368
• 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，极低剂量（1杯/公斤，静脉注射）可以