CORTICOSTERONE AND STRESSOR/COCAINE INTERACTIONS

与发病和发病相反的因素的特征 坚持强迫吸毒行为对老年人来说至关重要 构建有效的药物滥用治疗策略。同样， 确定这些因素相互作用的机制 有了这样的行为，才有利于潜能的开发 药物治疗剂。本提案中描述的实验 是为了研究压力和压力之间的相互作用 环境刺激、肾上腺皮质激素对可卡因的刺激作用 并且因此可提供底物，环境可通过该底物 影响这一行为。四个具体的AMIS设计来测试这一点 假设在这一提议中被勾勒出来。该计划的目的是 在具体目标1中提出的实验是确定类型的作用 I型和II型肾上腺皮质激素受体在趋化作用中的作用 皮质酮静脉注射可卡因。的作用 可卡因决定性刺激中的皮质酮和 应激诱导的可卡因泛化将在#年进行调查 特定目标2使用皮质酮合成抑制剂， 酮康唑。特定的Aim3由设计用来评估 有条件地恢复可卡因自我给药 慢性灭绝后的压力源。皮质酮在血管紧张素系统中的作用 这次复职将使用酮康唑进行调查。中的更改 慢性可卡因后的I型和II型受体 自我管理将在#年提出的实验中进行研究 具体目标4.

The characterization of factors that contrbute to the onset and persistence of compulsive drug-seeking behavior is crucual for the constrution of effective treatment strategies for drug abuse. Likewise, the determination of the mechanisms through which these factors interact with this behavior is petinent to the development of potential pharmacotherapeutic agenits. The experiments described in this proposal are designes to investigate the interaction between stressful environmental stimuli, adrenocorticosteroids stimulus effects of cocaine and therefore may provide a substrate through which the environment may influence this behavior. Four specific amis designes to test this hypothesis are outlines in this proposal. The purpose of the experiments proposed in Specific Aim 1 is to determine the role of Type I and Type II adrenocorticosteroid receptors in the favilitation on intravenous cocaine self-administration by cortocosterone. The role of corticosterone in the determinative stimulus of cocaine and in the stressor-induced generalization to cocaine will be investigated in Specific Aim 2 using the corticosterone synthesis inhibitor, keteconzole. Specific Aim3 consists of experiments desgined to assess the reinstatement of cocaine self-administration by a conditioned stressor following chronic extinction. The role of corticosterone in this reinstatement will be investigated using ketoconozole. Changes in Type I and Type II receptors following chronic cocaine self-administration will be investigated in experiments proposed in Specific Aim 4.