BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

拟议的调查旨在描述和区分一个 5-羟色胺能药物滥用的一组，其性质如下 歧视性刺激。重点将放在迷幻剂上 吲哚/苯乙胺类型，包括麦角酸二乙胺(LSD)和 2，5-二甲氧基-4-甲基苯丙胺(DOM)。此外，老鼠将被 用氯苯哌嗪[MCPP]进行训练，这是一种被广泛用作探针的药物 人类的5-羟色胺能活动。经过MCPP培训的受试者将 在评估5-HT1C的功能重要性时特别有用 感受器。以便为生物化学基础的研究奠定基础 它们的刺激作用，这些药物的特征将是 尊重它们与5-羟色胺能和其他选定受体的亲和力 在中枢神经系统和它们的改变能力方面 第二信使系统。 综上所述，利用强大的方法对体内进行评估 药效(药物歧视)，体外药效[刺激或 抑制第二信使形成]，以及特定的亲和力 受体(放射性配基结合)将提供对该模式的新理解 5-羟色胺能药物的作用，尤其是那些容易被滥用的药物。因此， 生化和行为实验将并行进行。一个 拟议研究的长期目标是实现 从生化的角度理解这些复杂的行为事件 动物，从而促进合理的治疗干预 人类。

The proposed investigation seeks to characterize and to distinguish a group of serotonergic drugs of abuse in terms of their properties as discriminative stimuli. Emphasis will be upon hallucinogens of the indole/phenethylamine type including lysergic acid diethylamide (LSD] and 2,5-dimethoxy-4-methyl-amphetamine (DOM). In addition, rats will be trained with chlorophenylpiperazine [MCPP], a drug widely used as a probe of serotonergic activity in humans. MCPP-trained subjects will be particularly useful in assessing the functional importance of 5-HT1C receptors. In order to lay a groundwork for the biochemical basis for their stimulus effects, these same drugs will be characterized with respect to their affinities for serotonergic and other selected receptors in the central nervous system and with respect to their ability to alter second messenger systems. 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 serotonergic drugs, especially those subject to abuse. Thus, biochemical and behavioral experiments will be conducted in parallel. A long-term objective of the proposed research is to achieve an understanding in biochemical terms of these complex behavioral events in animals and thus to facilitate rational treatment interventions for humans.