INTERACTIONS BETWEEN SIGMA AND NMDA RECEPTORS

最近的研究表明，极低的剂量(1杯/公斤，静脉注射)能 离子电泳法的NMDA兴奋效应大约是NMDA的两倍 适用于海马区(CA3)锥体神经元。此外，NMDA 拮抗剂CPP可抑制葡萄糖利用率的增加 由Sigma配体DTG(1 mg/kg，i.p.)产生，CPP阻断 DTG导致多巴胺释放增加的能力。基于这些 研究结果表明，西格玛配体(至少在某些情况下) 正向调节NMDA反应。三套实验是 建议进一步审查这一可能性，以便1)进一步 描述Sigma和NMDA在海马区的相互作用； 2)使用放射性配基结合技术来检查是否 相互作用可以在膜-受体水平上观察到。 相互作用；以及3)确定这些相互作用的一般性- 即检查在神经细胞中是否发现Sigma/NMDA相互作用 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 提示西格玛配体可以作为抗精神病药物，或者作为 抗精神病药物所致运动的药物治疗药物 精神错乱。此外，对海马体的研究可能已经 与学习和记忆的相关性，从而对某些 精神疾病，如阿尔茨海默病或其他疾病 影响心理健康。

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.