Drugs of Abuse and Human Aggressive Behavior

滥用药物和人类攻击行为

• 批准号: 7027837
• 负责人: Don R Cherek
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7027837
• 关键词: aggression; anticonvulsants; antisocial personality; behavior test; behavioral /social science research tag; benzodiazepines; clinical research; conduct disorder; drug interactions; gamma aminobutyrate; human subject; lorazepam; muscle relaxants; neurotransmitter agonist; neurotransmitter antagonist; psychopharmacology; violence

DESCRIPTION (provided by applicant): Aggressive behavior puts individuals at high risk for a variety of antisocial behaviors, including substance abuse and/or other criminal behavior. As a result, it is important to investigate some of the basic behavioral and pharmacological mechanisms which may affect and regulate aggressive behavior. For the past twenty years our laboratory has been engaged in the study of human aggressive responding under controlled conditions. We have developed a laboratory procedure, the Point Subtraction Aggression Paradigm (PSAP), which is now used in several laboratories in and outside the U.S. This phase our our research is looking at gamma aminobutyric acid (GABA) medications as potential interventions to decrease aggression as a venue which may influence future studies of pharmacotherapy of substance abuse. Determinations of acute drug administration will be conducted initially. If acute effects indicate relative selective suppression of aggressive responding, then chronic drug administration studies will be initiated. This continuation proposal will evaluate the acute and chronic effects of three GABAergic medications: baclofen, tiagabine and topiramate. Baclofen, an antispastic agent and a GABA-B agonist. Tiagabine, an anticonvulsant, is a selective GABA uptake inhibitor. Topiramate,an anticonvulsant, has a GABAergic effects involving different mechanisms. Based upon the broad range of possible clinical therapeutic targets for baclofen, tiagabine, and topiramate, we propose that the commonality for this pharmacological action is an effect upon impulse control disorders. Since aggression is not a recognized disorder, direct evaluation of these medications on aggressive behavior has not occurred. Clinical studies, although many are case reports and/or not well controlled, suggest possible usefulness in the following disorders: bulimia, binge eating, posttraumatic stress disorder, anxiety, mood disorders and the treatment of alcohol and substance abuse and dependence. Some of these disorders can in some instances be considered impulse disorders (alcoholism, substance abuse, bulimia and binge eating), while others may not have a clear association with impulse disorders but may be risk factor for such disorders, GABA as a major, if not the major, inhibitory system in the CNS, can be considered as an appropriate focus for pharmacological studies of impulse problem areas such as human aggression. The results of such studies may guide and supplement future clinical studies aimed at the suppression of human aggression, which may in turn impact other impulse problem behaviors.

描述（由申请人提供）：侵略行为使个人对各种反社会行为的高风险，包括滥用药物和/或其他犯罪行为。结果，重要的是研究一些可能影响和调节攻击行为的基本行为和药理机制。在过去的二十年中，我们的实验室研究了在受控条件下对人类侵略性反应的研究。我们已经开发了一种实验室程序，即点减法攻击范式（PSAP），该程序现已在美国外部和外部的几个实验室中使用，我们的研究正在研究伽马氨基丁酸（GABA）药物作为潜在的干预措施，以减少侵略性的侵略，这可能会影响物质滥用药物治疗的未来研究。急性药物给药的确定最初将进行。如果急性效应表明对侵略性反应的相对选择性抑制，则将开始慢性药物管理研究。该延续提案将评估三种GABA能药物的急性和慢性作用：巴氯氟芬，tiagabine和tupiramate。 Baclofen，一种反弹药剂和GABA-B激动剂。 Tiagabine是一种抗惊厥药，是一种选择性的GABA摄取抑制剂。托吡酯是一种抗惊厥药，具有涉及不同机制的GABA能作用。基于巴氯芬，黄氯芬和托吡酯的广泛临床治疗靶标，我们建议这种药理作用的共同点对脉冲控制疾病有效。由于侵略不是公认的疾病，因此对这些药物对侵略行为的直接评估尚未发生。临床研究虽然许多是病例报告和/或不受控制的临床研究，但表明在以下疾病中可能有用：贪食症，暴饮暴食，创伤后应激障碍，焦虑症，情绪障碍以及对酒精和药物滥用和依赖的治疗。在某些情况下，其中一些疾病可能被认为是冲动障碍（酒精中毒，滥用药物，贪食症和暴饮暴食），而其他疾病可能不会与冲动障碍有明显的联系，但可能是这种疾病的风险因素，GABA是主要的，如果不是CN中的主要，抑制系统，则可以将其视为适合人为攻击人类的愤怒领域。此类研究的结果可能指导和补充旨在抑制人类侵略的未来临床研究，这反过来可能会影响其他冲动问题行为。