BEHAVIORAL & PHARMACOLOGICAL ANALYSIS OF DRUGS OF ABUSE

拟议的调查旨在描述和区分 一组滥用的肾上腺素能药物，就其性质而言， 辨别性刺激 重点将放在致幻剂的 吲哚/苯乙胺型，包括麦角酰二乙胺（LSD）， 2，5-二甲氧基-4-甲基-苯丙胺（DOM）。 此外，老鼠将 用氯苯基哌嗪[MCPP]训练，一种广泛用作探针的药物 在人体内的肾上腺素能活动。 MCPP培训的受试者将 特别适用于评估5-HT 1C的功能重要性 受体。 为了奠定生物化学基础， 它们的刺激作用，这些相同的药物将具有 就其对肾上腺素能受体和其它选定受体的亲和力而言 在中枢神经系统中， 第二信使系统 总之，使用强大的方法进行体内评估， 功效（药物辨别），体外功效[刺激或 抑制第二信使的形成]，以及特异性 受体（放射性配体结合）将提供新的理解模式 对肾上腺素能药物的作用，特别是那些容易滥用的药物。 因此，在本发明中， 生化和行为实验将同时进行。 一 拟议研究的长期目标是实现 从生物化学的角度来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.