OPIOID RECEPTORS REGULATE STRIATAL GLUTAMATE EFFLUX

描述（申请人摘要）： 本提案的目的是研究kappa的调节， 突触体中纹状体谷氨酸流出的δ阿片受体 使用NADPH连接的荧光测定法。 精神兴奋剂诱发的运动活动 被谷氨酸受体拮抗剂和κ阿片类药物阻断 受体激动剂和δ阿片受体拮抗剂。 因为 纹状体是精神兴奋剂诱导的行为效应的场所， κ和δ阿片受体在那里表达，结构是 是研究阿片类药物-阿片受体相互作用的理想工具。 第一 这项提议的目的是确定纹状体谷氨酸是否 外排受突触前κ阿片受体调节。 Kappa阿片 受体激活降低L-反式-PDC诱发的纹状体谷氨酸 体内水平和突触体中4-AP诱发的谷氨酸流出。 因此，我们将比较kappa受体激活对 由L-反式-PDC和4-AP诱发的谷氨酸流出。 第二个目标 这项建议的目的是确定谷氨酸流出是否受到调节， 由突触前δ阿片受体控制 因为胆碱能中间神经元 表达δ阿片受体mRNA和毒蕈碱激动剂减少 纹状体谷氨酸释放，我们预期δ受体阻断 将通过增加乙酰胆碱释放减少谷氨酸流出， 突触前位点 这些研究将为阿片类药物的调节提供信息 纹状体中谷氨酸流出的受体。 这些产生的数据 研究将提供深入了解阿片系统在 调节谷氨酸水平，这是 精神兴奋剂

DESCRIPTION (Applicant's Abstract): The goal of this proposal is to investigate the regulation by kappa and delta opioid receptors of striatal glutamate efflux in synaptosomes using NADPH-linked fluorometry. Psychostimulant-induced motor activity is blocked by glutamate receptor antagonists and by kappa opioid receptor agonists and delta opioid receptor antagonists. Because the striatum is a locus for psychostimulant-induced behavioral effects and kappa and delta opioid receptors are expressed there, the structure is ideal for investigating opioid-glutamatergic interactions. The first objective of this proposal is to determine whether striatal glutamate efflux is regulated by presynaptic kappa opioid receptors. Kappa opioid receptor activation decreases L-trans-PDC-evoked striatal glutamate levels in vivo and 4-AP-evoked glutamate efflux in synaptosomes. Therefore, we will compare the effects of kappa receptors activation on glutamate efflux evoked by L-trans-PDC and 4-AP. The second objective of this proposal is to determine whether glutamate efflux is regulated by presynaptic delta opioid receptors. Because cholinergic interneurons express delta opioid receptor MRNA and muscarinic agonists decrease striatal glutamate release, we expect that blockade of delta receptors will reduce glutamate efflux by increasing acetylcholine release from presynaptic loci. These studies will contribute information about the regulation by opioid receptors of glutamate efflux in the striatum. Data generated by these studies will provide insight into the role of opioid systems in the modulation of glutamate levels which underlie the actions of psychostimulants.