ADRENORECEPTOR FUNCTION AFTER CHRONIC OPIATE TREATMENT

这项研究的目的是刻画长期的 阿片类药物对中枢肾上腺素受体功能的影响 旨在澄清肾上腺素能机制在 调节与之相关的生理和行为变化 鸦片类药物滥用。放射性配基结合技术将用于评估 α1、α2和β的数量和/或亲和力的变化 慢性吗啡后大鼠特定脑区的肾上腺素受体 治疗，包括杏仁核，下丘脑，LC，顶叶皮质， 海马、孤束核和三叉神经脊束核 (STN)。虽然现在已经记录了皮层和大脑皮质中受体的变化 在慢性吗啡治疗动物的海马区，重要的是 确定在不同的边缘和脑干是否发生类似的变化 与节欲迹象的调解有关的结构。 细胞外记录和微压药物喷射研究将 在体内进行，与结合试验平行进行，以评估 突触后α和β受体变化的功能相关性 慢性吗啡后后四种结构中的每一种 行政管理。类似的分析随后将在体外扩展。 海马区和NTS脑片的细胞外和 细胞内记录方法结合洗浴灌流 毒品。突触前α2和β受体的功能变化 还将对长期吗啡治疗造成的影响进行评估。一个 这项研究工作的具体目的是检查 特定脑区肾上腺素受体功能的改变可能是 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。在解决这一问题时，试图 将被用来在时间上关联在 放射性配基结合与肾上腺素受体敏感性的关系 吗啡依赖与戒断症状的变化 跨越时间。为了进一步探讨这个问题，类似类型的分析 将在用U-50,488H，a慢性治疗动物后进行 不产生吗啡样物质的选择性kappa激动剂 依赖。拟议的研究，有助于我们理解 脑内肾上腺素能机制参与生理和心理状态 与阿片类药物滥用相关的行为变化可能有助于促进 治疗人类毒品依赖的有效新战略。

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.