Behavioral & Pharmacological Analysis of Drugs of Abuse

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• 批准号: 6778352
• 负责人: JERROLD Clyne WINTER
• 金额: $ 35.33万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778352
• 关键词: 2,5 dimethoxy 4 methylamphetamine; NMDA receptors; autoradiography; clozapine; drug abuse; drug interactions; drug receptors; gas chromatography mass spectrometry; glutamate receptor; glutamates; inhibitor /antagonist; laboratory rat; lysergic acid diethylamide; neuropharmacology; psychopharmacology; receptor expression; serotonin; serotonin inhibitor; substance abuse related behavior

The discovery by Albert Hofmann more than fifty years ago of the hallucinogenic effects of LSD irreversibly altered the course of both biological psychiatry and popular culture. Hallucinogens of all types are subject to widespread and increasing abuse by adolescents and young adults in this country. For example, in 1998 use of hallucinogens exceeded that of cocaine in the age groups 12-17 and 18-25. Indeed, hallucinogens were more commonly ingested than tranquilizers, inhalants, and sedatives combined. Furthermore, LSD was identified in 1999 as a "club drug" in the campaign by the National Institute on Drug Abuse to alert the public to the hazards of these agents. In addition to the well recognized abuse liability of these drugs, hallucinogens are perhaps unique in that an understanding of their mechanisms of action would contribute not only to an amelioration of the burdens of illicit use but might also provide a key to solving the puzzle of psychosis, another major human affliction. The present investigations seek to characterize indoleamine hallucinogens such as LSD and phenethylamine hallucinogens as exemplified by DOM in combined behavioral, biochemical, and analytical [GC-MS] studies. Specifically, studies will also examine the neuroanatomical sites involved in hallucinogen- induced stimulus control. In addition, experiments will further characterize interactions between the serotonergic and glutamatergic systems in the brain. Finally, the mechanisms responsible for the potentiation of LSD and other hallucinogens by fluoxetine and related selective serotonin reuptake inhibitors will be examined. Taken together, the correlational use of powerful methods for the assessment of in vivo and in vitro efficacy and of brain levels of DOM and of neurotransmitters will provide new understanding of the mode of action of hallucinogens.

50多年前，阿尔伯特·霍夫曼发现了LSD的致幻作用，这一发现不可逆转地改变了生物精神病学和流行文化的进程。在这个国家，所有类型的致幻剂都受到青少年和年轻人的广泛和日益增长的滥用。例如，1998年，在12-17岁和18-25岁年龄组中，致幻剂的使用超过了可卡因。 事实上，致幻剂的摄入量比镇静剂、吸入剂和镇静剂的总和还要多。 此外，国家药物滥用研究所在1999年开展的一项运动中将迷幻剂确定为“俱乐部药物”，以提醒公众注意这些制剂的危害。 除了公认的滥用这些药物的倾向外，致幻剂的独特之处可能在于，了解其作用机制不仅有助于减轻非法使用的负担，而且还可能为解决精神病这一人类的另一种主要痛苦之谜提供一把钥匙。目前的调查试图表征吲哚胺类致幻剂，如LSD和苯乙胺类致幻剂，以DOM为例，结合行为，生物化学和分析[GC-MS]研究。 具体来说，研究还将检查涉及致幻剂诱导的刺激控制的神经解剖学部位。 此外，实验将进一步表征大脑中的多巴胺能和多巴胺能系统之间的相互作用。 最后，将研究氟西汀和相关的选择性5-羟色胺再摄取抑制剂增强LSD和其他致幻剂的机制。 两者合计，相关使用强大的方法来评估在体内和体外的疗效和脑水平的DOM和神经递质将提供新的理解的迷幻剂的作用方式。