BEHAVIORAL AND PHARMACOLOGIC ANALYSIS OF DRUG OF ABUSE

滥用药物的行为和药理学分析

• 批准号: 6175201
• 负责人: JERROLD Clyne WINTER
• 金额: $ 23.33万
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6175201
• 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; substance abuse related behavior

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） 50多年前，阿尔伯特·霍夫曼发现了 LSD的致幻作用不可逆转地改变了两者的过程， 生物精神病学和流行文化。 霍夫曼的遗产之一是 1996年8月全国住户调查预先报告中发现， 药物滥用，其中显示使用致幻剂的人数急剧增加， 12-17岁的儿童;毫无疑问，致幻剂是毒品 虐待 但在滥用的药物中，致幻剂可能是独一无二的， 了解它们的作用机制不仅可以改善 非法使用的负担，但也可能提供一个解决难题的关键 精神病，另一个人类的主要痛苦。 目前的调查试图描述和区分 吲哚胺致幻剂，如LSD和苯乙胺致幻剂， 以联合行为[药物诱导刺激控制]中的DOM为例 和生物化学[放射性配体结合和第二信使]研究。 具体来说，拟议中的实验将确定第二信使 介导LSD和DOM的辨别刺激效应的系统， 此外，还将鉴定那些可能调节 致幻剂的效果 这些研究还将扩大到 包括相关的吲哚胺致幻剂、5-甲氧基-DMT和伊波替尼。 最后，氟西汀对LSD和其他致幻剂的增效作用， 将检查相关的选择性5-羟色胺再摄取抑制剂。 采取 总之，使用强有力的方法来评估体内功效 [drug识别]，体外功效[刺激或抑制 第二信使形成]，以及对特定受体的亲和力 [放射性配体结合]将提供对作用模式的新理解 致幻剂