SELF INJURIOUS BEHAVIOR AND PRIMATE WELL BEING

自残行为与灵长类动物的健康

• 批准号: 6194754
• 负责人: Melinda Ann Novak
• 金额: $ 37.83万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6194754
• 关键词: Macaca mulatta; adrenocorticotropic hormone; aggression; animal welfare research; arousal; behavioral /social science research tag; behavioral genetics; corticosteroid receptors; corticotropin releasing factor; cortisol; ethology; fenfluramine; gene expression; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; prolactin; psychological stressor; psychopharmacology; quality of life; receptor binding; receptor expression; self destructive behavior; serotonin; serotonin receptor; wakefulness

Primates, such as Old World monkeys, represent a crucial research resource, and major scientific advances in medicine, biology, and neuroscience can be attributed to their use. Despite the recent strides made in controlling colony diseases, in developing new housing regimens, and in modernizing facilities, some monkeys develop pathological behavior. Of particular concern is the small but persistent percentage of monkeys that develop the syndrome of self-injurious behavior (SIB). The occurrence of SIB compromises the goal of promoting the physical and psychological well-being of laboratory primates as mandated by the Animal Welfare Act (Revised 1991). It also threatens the quality of the monkey research resource, particularly because monkeys with this condition differ both behaviorally and physiologically from other monkeys in the colony. Our research has shown that monkeys with SIB are more aggressive, are more likely to have experienced early social separation, and have been exposed to more stressful events than normal monkeys. Monkeys with this disorder also show altered heart rate patterns and a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis manifested by unusually low levels of plasma cortisol. This pattern of precipitating stressors and low cortisol parallels similar observations in patients with post-traumatic stress disorder (PTSD). The continuing objective of this project is to characterize the nature of SIB in rhesus monkeys, to identify the mechanisms responsible for this behavioral pathology, and to devise effective treatment regimens. Our current focus is on the HPA and serotonergic systems, both of which may be altered in monkeys with SIB. We will use various endocrine challenges to determine whether monkeys with SIB show reduced adrenocortical responsivity and heightened sensitivity of the glucocorticoid negative feedback system as is observed in PTSD patients. We will determine whether monkeys with SIB show altered stress responses to various social situations using our newly developed procedure of noninvasive collection of salivary cortisol in unrestrained adult animals. We will investigate cardiac and HPA reactions that surround spontaneous episodes of self-directed biting in an effort to determine whether biting serves as a coping strategy to reduce arousal. Other studies will examine the role of the serotonergic system in the expression of SIB by measuring hormonal responses to a fenfluramine challenge. Finally, we will evaluate the efficacy of serotonergic drugs as potential pharmacotherapeutic agents for reducing the incidence of SIB. These studies should provide important new information concerning the pathophysiology of SIB in monkeys and should lead to the development of useful treatment strategies.

诸如旧世界猴子之类的灵长类动物代表着重要的研究资源，医学，生物学和神经科学方面的重大科学进步可以归因于它们的使用。 尽管最近在控制菌落疾病，开发新的住房方案以及现代化设施方面取得了进步，但一些猴子发展了病理行为。 特别关心的是发展自我伤害行为综合征（SIB）的猴子的少量但持续的百分比。 SIB的发生损害了促进《动物福利法》规定的实验室灵长类动物的身体和心理健康的目标（修订1991年）。 它还威胁着猴子研究资源的质量，尤其是因为具有这种疾病的猴子在行为和生理上与殖民地的其他猴子都不同。 我们的研究表明，带有SIB的猴子更具侵略性，更有可能经历早期的社会分离，并且与正常猴子相比，经历了更紧张的事件。 患有这种疾病的猴子还显示出因异常低的血浆皮质醇表现出的下丘脑 - 垂体 - 肾上腺（HPA）轴的失调。 在创伤后应激障碍（PTSD）患者中，这种沉淀应激源和低皮质醇相似的模式相似。 该项目的持续目标是表征恒河猴中SIB的性质，以确定对这种行为病理学负责的机制，并设计有效的治疗方案。 我们目前的重点是HPA和血清素能系统，这两者都可能在使用SIB的猴子中改变。 我们将使用各种内分泌挑战来确定带有SIB的猴子是否表现出降低的肾上腺皮质反应性和糖皮质激素负反馈系统的灵敏度的提高，如PTSD患者所观察到的那样。 我们将使用我们新开发的无创的唾液皮质醇在不受约束的成年动物中收集新开发的程序，确定带有SIB的猴子对各种社交情况的压力反应发生了改变。 我们将研究心脏和HPA反应，这些反应围绕着自我指导的咬合的自发发作，以确定咬人是否可以作为减少唤醒的应对策略。 其他研究将通过测量对芬氟拉明挑战的荷尔蒙反应来研究血清素能系统在SIB表达中的作用。 最后，我们将评估血清素能药物作为降低SIB发病率的潜在药物治疗剂的疗效。这些研究应提供有关猴子中SIB病理生理学的重要新信息，并应导致有用的治疗策略的发展。