ADRENORECEPTOR FUNCTION AFTER CHRONIC OPIATE TREATMENT

这项研究的目的是描述长期 阿片类药物对中枢肾上腺素受体功能的影响， 旨在阐明肾上腺素能机制在 调解与之相关的生理和行为变化， 滥用鸦片 放射性配体结合技术将用于评价 α 1、α 2和β的数量和/或亲和力的变化 慢性吗啡依赖大鼠特定脑区的肾上腺素受体 治疗，包括杏仁核，下丘脑，LC，顶叶皮层， 海马、孤束核和三叉神经脊束核 （二）。 虽然现在已经记录了大脑皮层和海马中受体的变化， 海马在慢性吗啡治疗的动物，这将是重要的， 确定是否类似的改变发生在各种边缘系统和脑干 这些结构与禁欲标志的调解有关。 细胞外记录和微压药物喷射研究将在 与结合测定平行在体内进行，以评估 突触后α和β受体变化的功能相关性 在慢性吗啡给药后的后四种结构中， 局 然后将在体外试验中进行类似的分析。 海马和NTS切片制备使用细胞外和 细胞内记录方法结合浴灌流， 毒品 突触前α 2和β受体的功能变化 还将评估长期吗啡治疗的结果。 一 这项研究工作的具体目标是研究以下可能性： 特定脑区肾上腺素受体功能的变化可能是 参与阿片类药物依赖的形成和/或在 阿片类药物戒断的表现 为了解决这个问题， 将在时间上关联变化的发生， 放射性配体结合和肾上腺素受体敏感性， 吗啡依赖和戒断体征的变化 穿越时空 为了进一步探讨这个问题，类似的分析 将在用U-50，488 H，a 不产生吗啡样物理活性的选择性κ激动剂 依赖 建议的研究，有助于我们了解 脑肾上腺素能机制参与生理和 与阿片类药物滥用相关的行为变化，可能有助于促进 治疗人类麻醉品依赖性的有效新策略。

The goal of this research is to characterize the effects of long-term opiate administration on central adrenoreceptor function, with an overall effort aimed at clarifying the role of adrenergic mechanisms in the mediation of the physiological and behavioral changes associated with opiate abuse. Radioligand binding techniques will be used to evaluate changes in the number and/or affinity of alpha1, alpha2, and beta adrenoreceptors in specific brain areas in rats following chronic morphine treatment, including the amygdala, hypothalamus, LC, parietal cortex, hippocampus, nucleus tractus solitarius (NTS) and spinal trigeminal nucleus (STN). While receptor changes have now been documented in cortex and hippocampus in chronic morphine-treated animals, it will be important to determine whether similar alterations occur in various limbic and brainstem structures which have been linked to the mediation of abstinence signs. Extracellular recording and micropressure drug ejection studies will be carried out in vivo in parallel with the binding assays to assess the functional correlates of changes in postsynaptic alpha and beta receptors in each of the latter four structures following chronic morphine administration. Similar analyses will then be extended in the in vitro hippocampal and NTS slice preparations using both extracellular and intracellular recording methods in combination with bath superfusion of drugs. Functional changes in presynaptic alpha2 and beta receptors resulting from long-term morphine treatment will also be assessed. A specific aim of this research effort is to examine the possibility that changes in adrenoreceptor function in specific brain regions may be involved in the formation of opiate dependence and/or figure prominently in the manifestation of opiate withdrawal. In addressing this issue, attempts will be made to temporally correlate the occurrence of changes in radioligand binding and adrenoreceptor sensitivity with the emergence of dependence on morphine and with changes in the profile of abstinence signs across time. To further explore this question, similar types of analyses will be performed following chronic treatment of animals with U-50, 488H, a selective kappa agonist which does not produce morphine-like physical dependence. The proposed research, in contributing to our understanding of the involvement of brain adrenergic mechanisms in the physiological and behavioral changes associated with opiate abuse, might help to promote effective new strategies in the treatment of narcotic dependency in man.