SELF INJURIOUS BEHAVIOR AND PRIMATE WELL BEING

自残行为与灵长类动物的健康

• 批准号: 6763090
• 负责人: Melinda Ann Novak
• 金额: $ 36.5万
• 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/6763090
• 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.

灵长类动物，如东大陆猴，是一种重要的研究资源，医学、生物学和神经科学领域的重大科学进步都可以归功于它们的使用。 尽管最近在控制群体疾病、开发新的饲养方案和现代化设施方面取得了长足进步，但一些猴子还是出现了病态行为。 特别值得关注的是，患有自残行为综合症（SIB）的猴子比例虽小，但持续存在。 SIB 的发生损害了《动物福利法》（1991 年修订）所规定的促进实验室灵长类动物身心健康的目标。 它还威胁到猴子研究资源的质量，特别是因为患有这种疾病的猴子在行为和生理上都与群体中的其他猴子不同。 我们的研究表明，患有 SIB 的猴子比正常猴子更具攻击性，更有可能经历过早期的社会分离，并且经历过更多的压力事件。 患有这种疾病的猴子还表现出心率模式改变和下丘脑-垂体-肾上腺（HPA）轴失调，表现为血浆皮质醇水平异常低。 这种诱发压力源和低皮质醇的模式与创伤后应激障碍（PTSD）患者的类似观察结果相似。 该项目的持续目标是描述恒河猴​​ SIB 的性质，确定导致这种行为病理学的机制，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，这两个系统在患有 SIB 的猴子中都可能发生改变。 我们将使用各种内分泌挑战来确定患有 SIB 的猴子是否表现出肾上腺皮质反应性降低和糖皮质激素负反馈系统的敏感性升高，正如在 PTSD 患者中观察到的那样。 我们将使用我们新开发的无创性收集不受约束的成年动物唾液皮质醇的程序，确定患有 SIB 的猴子是否对各种社交情境表现出不同的应激反应。 我们将调查围绕自发性咬伤事件的心脏和 HPA 反应，以确定咬伤是否可以作为减少兴奋的应对策略。 其他研究将通过测量对芬氟拉明激发的激素反应来检查血清素能系统在 SIB 表达中的作用。 最后，我们将评估血清素药物作为潜在药物治疗剂降低 SIB 发病率的功效。这些研究应该提供有关猴子 SIB 病理生理学的重要新信息，并有助于制定有用的治疗策略。