BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

行为的

• 批准号: 3207876
• 负责人: JERROLD Clyne WINTER
• 金额: $ 8.05万
• 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 1987-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3207876
• 关键词: 5 hydroxytryptophan; adrenergic agents; dosage; lysergic acid diethylamide; operant conditionings; psychotomimetic drug; radiotracer; serotonin; serotonin inhibitor; stimulus /response; stimulus generalization

Nearly all drugs of abuse are able to assume stimulus control in animals. This fact provides a sensitive and informative approach to the study of the mechanism of action of a variety of drugs habitually chosen for non-medical use by humans. On a different organizational level, recent developments in radioligand binding techniques have made it possible to identify and characterize the receptors for many drugs and endogenous neurotransmitters. The proposed investigation combines drug-induced stimulus control with receptor binding in a study of hallucinogens of the indoleamine type; drugs which are, for a variety of reasons, thought to exert their actions via 5-hydroxytryptamine (5-HT). 5-HT is widely believed to function as a neurotransmitter and to play a significant role in a variety of behaviors including sleep, sexual activity, appetite, mood, and psychosis. It is the changes in mood and perception that are responsible for the primary reinforcing properties, hence the abuse liability, of indoleamine hallucinogens such as LSD. In the proposed investigation, a variety of drugs thought to act as 5-HT agonists or antagonists will be studied in animals trained to discriminate the effects of either LSD or 5-HTP, the amino acid precursor of 5-HT. Each drug will be characterized as either an agonist or an antagonist and, based on its dose-response curve, either the ED50 or the AD50 will be calculated. Concomitantly, the binding of each drug to the 5-HT1 receptor in rat hippocampal tissue ((3H)5-HT) and the 5-HT2 receptor in rat cortical tissue (3H)ketanserin) will be measured. The affinities of the drugs will be determined by analysis of competition curves. Finally, the behavioral and receptor-binding data will be combined in a series of correlations, e.t., between the ED50's of agonists substituting for LSD and their affinities for the 5-HT1 receptor. In this way, the relative role of the receptor subtypes in the behavioral effects of the drugs will be determined. It is expected that the direct comparison of behavioral activities with reference to LSD, an exogenous 5-HT agonist, and 5-HTP, precursor for the endogenous agonist, will be particularly informative in that the pharmacological effects of LSD and 5-HTP are markedly different in humans.

几乎所有滥用药物都能在动物身上承担刺激控制作用。 这一事实提供了一种敏感和信息丰富的方法来研究 几种习惯性非医用药物的作用机制 供人类使用。在不同的组织层面上，最近在 放射性配基结合技术使识别和识别和 描述多种药物的受体和内源性神经递质。 这项拟议的研究将药物诱导的刺激控制与 吲哚胺类致幻剂研究中的受体结合；药物 出于各种原因，它们被认为通过 5-羟色胺(5-HT)。5-羟色胺被广泛认为是一种 神经递质和在各种行为中发挥重要作用 包括睡眠、性行为、食欲、情绪和精神病。它是 情绪和知觉的变化是导致初发期的 增强吲哚胺的性质，从而增加滥用的可能性 迷幻剂，如LSD。在拟议的调查中，各种 被认为是5-羟色胺激动剂或拮抗剂的药物将在 经过训练以辨别LSD或5-HTP影响的动物， 5-羟色胺的氨基酸前体。每种药物都将被描述为 激动剂或拮抗剂，根据其剂量-反应曲线， ED50或AD50将被计算。随之而来的是，每个 药物对大鼠海马区5-羟色胺受体的影响 测定大鼠皮质组织中5-HT2受体(~H)酮丝氨酸的含量。 药物的亲和力将通过竞争分析来确定。 曲线。最后，行为数据和受体结合数据将被合并 在一系列相关性中，E.T.，激动剂的ED50‘S 取代LSD及其与5-HT1受体的亲和力。在这 受体亚型在行为效应中的相对作用 药物的种类将会被确定。预计直接比较 与外源性5-羟色胺激动剂LSD有关的行为活动， 而内源性激动剂的前体5-HTP将特别 LSD和5-HTP的药理作用是 在人类身上有明显的不同。