Behavioral and Pharmacological Analysis of Drugs of Abuse

6.项目摘要/摘要 所有类型的迷幻剂都会被广泛滥用，特别是青少年和 这个国家的年轻人。也许同样重要的是，这些药物可能会 提供最严重形式的精神疾病的病因学线索。长期目标 本提案的目的是描述致幻剂的行为和药理学特征 最终目标是建立他们的行动机制。尽管他们是由一个 通常的术语是迷幻剂，这些药物代表着不同的药理实体。麦角能 酸性二乙胺[LSD]在化学和药理上与更简单的 以DMT和裸盖菇素为代表的吲哚胺类化合物。事实上，就假定的受体而言 致幻作用的机制，LSD更类似于苯乙胺，如 梅斯卡林。尽管如此，所有这些药物都通过5-羟色胺能[5- 羟色胺能机制。直到最近，情况才有所不同。 苯环利定[五氯苯酚，天使粉]然而，一个统一的5-羟色胺-谷氨酸能机制是 开始出现这样的假设，即谷氨酸释放可能代表最终的共同 迷幻剂的路径。尽管如此，要说所有这些药物都以某种方式 5-羟色胺能本质上掩盖了这样一个事实，即已知14个不同的5-羟色胺能受体，每个受体 具有明显的神经解剖分布和一系列功能。决定把重点放在 目前关于5-HT2C，5-HT7，5-HT2~a，n d 5-HTqAr受体的建议是基于 药理学和行为学证据，将这些受体与幻觉发生联系起来。这个 主要的行为指标将继续是迷幻剂对啮齿动物的刺激作用， 人们普遍认为，这些影响与人类的主观因素密切相关。此外, 致幻剂的特征将使用体内微透析来关联谷氨酸的释放 与行为活动有关。预计整合所产生的数据将提供新的 了解迷幻剂的作用模式，特别是那些容易被滥用的迷幻剂。在……里面 此外，这些研究可能有助于我们理解最严重的精神状态 疾病包括焦虑、抑郁和精神错乱。最后，互联网在这方面的作用 对这些和其他俱乐部毒品，如摇头丸[摇头丸]的兴趣不断扩大，特别是在 社会的年轻群体是不可估量的，但几乎肯定会导致非法使用的增加。 这种可能性再加上对药物治疗用途的持续兴趣，例如 裸盖菇素对这些药物进行了详细的药理学评估，这是至关重要的。

6. Project Summary/Abstract Hallucinogens of all types are subject to widespread abuse especially by adolescents and young adults in this country. Perhaps equally important is the possibility that these drugs may offer clues to the etiology of the most serious forms of mental illness. The long-term objectives of the present proposal are to characterize hallucinogens behaviorally and pharmacologically with the ultimate goal of establishing their mechanisms of action. Although they are united by a common term, hallucinogen, these drugs represent distinct pharmacological entities. Lysergic acid diethylamide [LSD] is chemically and pharmacologically quite different from the simpler indoleamines represented by DMT and psilocybin. Indeed, in terms of a presumed receptor mechanism of hallucinogenic action, LSD more closely resembles a phenethylamine such as mescaline. Nonetheless, all of these drugs are joined by prominent activity via serotonergic [5- hydroxytryptaminergic] mechanisms. Until recently, the same could not be said for phencyclidine [PCP, Angel Dust]. However, a unifying serotonergic-glutamatergic mechanism is beginning to emerge with the hypothesis that glutamate release may represent a final common pathway for hallucinogens. Nonetheless, to say that all of these drugs are somehow serotonergic in nature obscures the fact that 14 distinct serotonergic receptors are known, each with a distinct neuroanatomic distribution and array of functions. The decision to focus in the present proposal on, 5-HT2c, 5-HT7, 5-HT2~a,n d 5-HTqAr eceptors is based upon suggestive pharmacological and behavioral evidence, which links these receptors to hallucinogenesis. The primary behavioral index will continue to be the stimulus effects of hallucinogens in rodents, effects widely believed to have significant subjective correlates in humans. In addition, hallucinogens will be characterized using in vivo microdialysis to correlate glutamate release with behavioral activity. It is expected that integration of the resulting data will provide new understanding of the mode of action of hallucinogens, especially those subject to abuse. In addition, these studies may contribute to our understanding of the most serious forms of mental illness including anxiety, depression, and psychosis. Finally, the role of the internet in expanding interest in these and other club drugs such as MDMA [Ecstasy] especially among youthful segments of society is inestimable but will almost certainly lead to increased illicit use. This likelihood coupled with continued interest in the therapeutic use of agents such as psilocybin makes a detailed pharmacological assessment of these drugs of utmost importance.