OPIOID RECEPTORS REGULATE STRIATAL GLUTAMATE EFFLUX

描述(申请人摘要)： 这项提案的目标是调查卡帕和 突触体内纹状体谷氨酸外流的阿片受体 使用NADPH连接的荧光法。精神刺激剂诱发的运动活动 被谷氨酸受体拮抗剂和kappa阿片类药物阻断 受体激动剂和增量阿片受体拮抗剂。因为 纹状体是心理刺激剂诱导的行为效应的场所， Kappa和Delta阿片受体在那里表达，结构是 非常适合研究阿片-谷氨酸能相互作用。第一 这项建议的目的是确定纹状体谷氨酸 外流受突触前kappa阿片受体调节。卡帕阿片类药物 受体激活降低L反式脱氧核糖核酸诱导的纹状体谷氨酸 体内水平和4-AP可引起突触体内谷氨酸外流。 因此，我们将比较kappa受体激活对 L-反式-PDC和4-AP引起的谷氨酸外流。第二个目标 这项建议的目的是确定谷氨酸外流是否受到监管 通过突触前三角洲阿片受体。因为胆碱能中间神经元 β-阿片受体基因表达减少，M受体激动剂减少 纹状体谷氨酸的释放，我们预计Delta型受体的阻断 将通过增加乙酰胆碱的释放来减少谷氨酸的外流 突触前轨迹。 这些研究将为阿片类药物的调节提供信息。 纹状体内谷氨酸外流的受体。由这些服务器生成的数据 研究将提供对阿片系统在 调节谷氨酸水平，这是其作用的基础 精神刺激剂。

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.