COCAINE EFFECTS ON CEREBRAL BLOOD FLOW--OXYGEN 15 PET

可卡因对脑血流的影响--OXYGEN 15 PET

• 批准号: 6245409
• 负责人: GODFREY D PEARLSON
• 金额: $ 2.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-05 至 1997-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6245409
• 关键词: blood flow measurement; clinical research; cocaine; dopamine antagonists; human subject; male; neuropharmacology; oxygen; positron emission tomography; psychopharmacology; radionuclides; radiotracer

Cocaine is a commonly abused euphoriant with strong reinforcing effects. Animal data have shown, that the reinforcing properties are related to cocaine's activity on the dopamine system including the transporter. We designed two Positron Emission Tomography studies (a) to investigate cocaine's activity on dopamine release in humans and (b) on regional cerebral blood flow. In study one, 11 male subjects were injected within [1 IC]-Raclopride, a positronemitting dopamine D2 antagonist. 0 to 10 minutes after the raclopride injection subjects were injected with either saline (baseline scan) or with 48mg of cocaine hydrochloride (drug scan). Time - Activity curves (TAC) were obtained for both conditions in putamen and cerebellum. In study two, three subjects were injected with 015 water 30 to 180 seconds after cocaine injection. All subjects reported subjective euphoriant effects on Visual Analog Scales. The area under the TAC (corrected for the amount of injected dose of radioactivity) was 251.0 1 39.1 in the cocaine condition (t=6.7, p<0.0001, df=10). In study two, global cerebral blood flow was reduced 27 1 9% using in three subjects. Maximal decreases were seen 60 seconds after cocaine injection. We demonstrated that doses of cocaine similar to typical "street doses" demonstrated significant displacement of a radiolabelled dopamine D2 receptor antagonist. This finding seems consistent with the dopamine hypothesis of cocaine's actions and is of potential relevance in the search for pharmacological treatments of cocaine abuse. Furthermore we replicated the finding of other studies, that cocaine reduces global blood flow acutely. Future Plans: Analyses of regional patterns of CBF changes as well as correlations with behavioral measures are under way, and we will continue to study subjects with 015 to better define the "time window" of cocaine effects and to plot dose response relationships within individuals.

可卡因是一种常被滥用的欣快剂，具有强烈的强化作用。 动物数据表明，增强性能与 可卡因对多巴胺系统包括转运蛋白的作用 我们设计了两项正电子发射断层扫描研究（a）来研究 可卡因对人体多巴胺释放的活性和（B）对局部多巴胺释放的活性 脑血流。 在研究1中，11名男性受试者被注射[1 IC]-雷氯必利， 正电子发射多巴胺D2拮抗剂。0至10分钟后， 雷氯必利注射受试者注射生理盐水（基线 扫描）或48毫克盐酸可卡因（药物扫描）。 时间-- 在壳核中获得两种条件下的活性曲线（TAC）， 小脑 在第二项研究中，三名受试者被注射了015水 注射可卡因后30到180秒。 所有受试者都报告了视觉模拟的主观欣快效应 鳞片 TAC下的面积（针对注射的量校正） 放射性剂量）在可卡因条件下为251.0 ± 39.1（t=6.7， p<0.0001，df=10）。 在第二项研究中， 三科用药率为2719%。 60秒时观察到最大下降 可卡因注射后。 我们证明了与典型的“街头剂量”相似的可卡因剂量 证明放射性标记的多巴胺D2 受体拮抗剂 这一发现似乎与多巴胺 可卡因的行动假设，并在潜在的相关性， 寻找可卡因滥用的药物治疗方法。 此外我们 重复了其他研究的发现，可卡因减少了全球 血液流动剧烈。 未来计划： CBF变化的区域模式及其相关性分析 行为措施正在进行中，我们将继续研究 015的受试者更好地定义可卡因效应的“时间窗” 并绘制个体内的剂量反应关系。