BEHAVIORAL AND PHARMACOLOGIC ANALYSIS OF DRUG OF ABUSE

滥用药物的行为和药理学分析

• 批准号: 2713059
• 负责人: JERROLD Clyne WINTER
• 金额: $ 21.99万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 2001-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2713059
• 关键词: 2,5 dimethoxy 4 methylamphetamine; 5 methoxy N,N dimethyltryptamine; behavior test; drug abuse; fluoxetine; hallucinogens; ibogaine; indoleamine; laboratory rat; lysergic acid diethylamide; neuropharmacology; pharmacokinetics; phenylethylamines; psychopharmacology; second messengers; serotonin inhibitor; serotonin receptor

DESCRIPTION: (Applicant's Abstract) The discovery by Albert Hoffmann more than fifty years ago of the hallucinogenic effects of LSD irreversibly altered the course of both biological psychiatry and popular culture. Part of Hofmann's legacy is found in the August 1996 Advance Report of the National Household Survey on Drug Abuse which shows a dramatic increase in the use of hallucinogens among children 12-17 years of age; without question, the hallucinogens are drugs of abuse. But among the drugs of abuse, hallucinogens are perhaps unique in that an understanding of their mechanisms of action will not only ameliorate the burdens of illicit use but may also provide a key to solving the puzzle of psychosis, another major human affliction. The present investigations seek to characterize and to distinguish indoleamine hallucinogens such as LSD and phenethylamine hallucinogens as exemplified by DOM in combined behavioral [drug-induced stimulus control] and biochemical [radioligand binding and second messenger] studies. Specifically, the proposed experiments will identify the second messenger systems which mediate the discriminative stimulus effects of LSD and DOM and will, in addition, identify those serotonergic receptors which may modulate the effects of hallucinogens. These studies will also be extended to include the related indoleamine hallucinogens, 5-methoxy-DMT and ibogaine. Finally, the potentiation of LSD and other hallucinogens by fluoxetine and related selective serotonin reuptake inhibitors will be examined. Taken together, the use of powerful methods for the assessment of in vivo efficacy [drug discrimination], of in vitro efficacy [stimulation or suppression of second messenger formation], and of affinities for specific receptors [radioligand binding] will provide new understanding of the mode of action of hallucinogens.

描述：(申请人摘要) 阿尔伯特·霍夫曼在50多年前发现了 LSD的致幻作用不可逆转地改变了两者的进程 生物精神病学和流行文化。霍夫曼留下的部分遗产是 载于1996年8月全国住户统计调查先期报告 药物滥用，表明迷幻剂的使用在 12-17岁的儿童；毫无疑问，致幻剂是毒品 滥用职权。但在滥用的药物中，迷幻剂可能是独一无二的 对它们的作用机制的了解不仅可以改善 非法使用的负担，但也可能提供解开谜团的钥匙 精神错乱，这是另一种主要的人类痛苦。 目前的调查试图描述和区分 吲哚胺类迷幻剂，如LSD和苯乙胺类迷幻剂 以DOM为例的组合行为[药物诱导的刺激控制] 以及生化[放射性配基结合和第二信使]研究。 具体地说，拟议的实验将识别第二个信使 调节LSD和DOM的歧视性刺激效应的系统和 此外，将识别那些可能调节5-羟色胺能受体 迷幻剂的作用。这些研究还将扩展到 包括相关的吲哚胺类致幻剂、5-甲氧基-DMT和伊波甘。 最后，氟西汀和其他致幻剂对LSD和其他致幻剂的增强作用 相关的选择性5-羟色胺再摄取抑制剂将被检查。已被占用 总之，使用强大的方法评估体内的疗效 [药物歧视]，体外疗效[刺激或抑制 第二信使形成]，以及特定受体的亲和力 [放射性配基结合]将提供对作用模式的新理解 迷幻剂。