BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

几乎所有的滥用药物都能在动物身上产生刺激控制。 这一事实提供了一个敏感和翔实的方法来研究的 通常选择用于非医疗用途的各种药物的作用机制 人类使用。 在不同的组织层面， 放射性配体结合技术使得有可能鉴定和 表征许多药物和内源性神经递质的受体。 拟议的调查结合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 由于各种原因，人们认为它们的作用是通过 5-羟色胺（5-HT）。 5-HT被广泛认为是一种 神经递质，并在各种行为中发挥重要作用 包括睡眠、性活动、食欲、情绪和精神病。 是 情绪和感知的变化，这是负责主要的 加强吲哚胺的性质，因此易被滥用 迷幻剂，如LSD。 在拟议的调查中， 被认为是5-HT激动剂或拮抗剂的药物将在 训练动物辨别LSD或5-HTP的效果， 5-HT的氨基酸前体。 每种药物将被表征为 激动剂或拮抗剂，并且基于其剂量-反应曲线， 将计算ED 50或AD 50。 与此同时，每个人的约束力 药物对大鼠海马组织5-HT_1受体（~ 3 H）5-HT）的作用及 将测量大鼠皮质组织中的5-HT 2受体（3 H酮色林）。 药物的亲和力将通过竞争分析来确定 曲线. 最后，将结合行为和受体结合数据 在一系列相关性中，e. t.，激动剂的ED 50 以及它们对5-HT 1受体的亲和力。 在这 受体亚型在行为效应中的相对作用 药物将被确定。 预计直接比较 行为活动与LSD有关，LSD是一种外源性5-HT激动剂， 和5-HTP，内源性激动剂的前体，将特别是 LSD和5-HTP的药理作用是有用的， 在人类身上有明显的不同。

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.