SEROTONIN AND AGGRESSION IN COCAINE DEPENDENCE

可卡因依赖中的血清素和攻击性

• 批准号: 6281712
• 负责人: FREDERICK Gerard MOELLER
• 金额: $ 1.36万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281712
• 关键词: aggression; behavioral /social science research tag; buspirone; child behavior disorders; clinical research; cocaine; drug addiction; drug withdrawal; human subject; human therapy evaluation; mental disorder chemotherapy; serotonin; violence

Cocaine dependence and violence are serious public health problems that are often related. There are many biological features of these behaviors that are poorly understood. Further research will elucidate mechanisms and contribute to the development of more effective treatments for impulsive behaviors including cocaine use and the associated violence. Low serotonin (5-HT) function is associated with increased aggressive and impulsive behavior in individuals with antisocial personality disorder (ASP). These same individuals have a high probability of substance dependence. Thus, the association between substance abuse and impulsive and aggressive behavior is complex and may be influenced both by the pharmacologic effects of drugs themselves and the fact that individuals who abuse drugs are also more prone to these behaviors. Although some studies find that cocaine increases aggressive behavior in laboratory animals, most animal studies do not find an increase in aggression after cocaine administration. Epidemiological studies find an association between cocaine and violence, but few laboratory studies have examined this issue in humans. In preliminary studies by our group, we have not found that acute doses of cocaine or recent chronic cocaine use increase aggressive responding in humans. The specific aims of this proposal are: Aim 1: To determine the effects of recent chronic cocaine use and cocaine abstinence/withdrawal on impulsive and aggressive responding in female and male cocaine dependent subjects with ASP with a history of childhood violent behavior, and in matched cocaine dependent subjects without ASP and to compare this responding to matched healthy controls. Aim 2: To measure 5-HT function using a neuroendocrine challenge and relate this measure to impulsive and aggressive responding in cocaine dependent subjects with ASP with a history of childhood violent behavior, in matched cocaine dependent subjects without ASP who have been off cocaine for at least two weeks and in healthy controls. Aim 3: To determine if chronic administration of the 5-HT agonist buspirone decreases impulsive and aggressive responding and cocaine use in subjects with ASP with a history of childhood violent behavior. Preliminary results from research performed thus far finds that: - Cocaine dependent subjects with a history of aggression in childhood are more aggressive on laboratory measures of aggression than those without this history. - Aggressive responding decreases as subjects withdraw from cocaine. - The amount of aggressive responding correlates with the severity of cocaine withdrawal symptoms.

可卡因依赖和暴力是严重的公共卫生问题 通常是相关的。 这些行为有许多生物学特征 理解很差。 进一步的研究将阐明机制 并为开发更有效的治疗做出贡献 冲动行为，包括可卡因的使用和相关的暴力行为。 低羟色胺（5-HT）功能与侵略性增加和 反社会人格障碍患者的冲动行为 （ASP）。 这些相同的人有很高的物质可能性 依赖。 因此，滥用药物与冲动之间的关联 侵略性行为很复杂，可能受到 药物本身的药理作用以及个人 滥用药物的人也更容易受到这些行为。 尽管一些研究发现可卡因在 实验室动物，大多数动物研究没有发现增加 可卡因给药后的侵略性。 流行病学研究发现 可卡因与暴力之间的关联，但是很少有实验室研究 在人类中检查了这个问题。 在我们小组的初步研究中，我们 尚未发现可卡因的急性剂量或最近的慢性可卡因使用 增加对人类的积极反应。 该提案的具体目的是： 目标1：确定最近使用可卡因和可卡因的影响 对女性的冲动和积极反应的禁欲/撤回 雄性可卡因依赖于ASP具有童年史的受试者 暴力行为，以及在没有ASP的匹配的可卡因依赖受试者中 并将这种响应与匹配的健康对照进行比较。 目标2：使用神经内分泌挑战测量5-HT功能， 将这一措施与可卡因的冲动和积极反应联系起来 具有儿童暴力行为史的ASP的依赖受试者， 在没有ASP的匹配的可卡因依赖性主题中 可卡因至少两个星期，并在健康对照组中。 目标3：确定5-HT激动剂的慢性给药是否 丁螺酮降低了冲动和侵略性的反应和可卡因的使用 具有儿童暴力行为史的ASP的受试者。 迄今为止所进行的研究的初步结果发现： - 可卡因依赖性受试者，具有儿童侵略史 比实验室的攻击措施更具侵略性 没有这个历史。 - 随着受试者退出可卡因，积极反应减少。 - 积极反应的量与严重程度相关 可卡因戒断症状。