Self-Injurious Behavior and Primate Well-Being

自残行为和灵长类动物的福祉

• 批准号: 6965605
• 负责人: Melinda Ann Novak
• 金额: $ 41.7万
• 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 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6965605
• 关键词: Macaca mulatta; adrenocorticotropic hormone; animal welfare research; anxiety; behavioral /social science research tag; behavioral genetics; biomarker; cortisol; ethology; experience; gene expression; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; mental disorder chemotherapy; opioid receptor; psychological stressor; psychopharmacology; quality of life; receptor expression; receptor sensitivity; self destructive behavior; stress

DESCRIPTION (provided by applicant): Rhesus monkeys are a crucial research resource, and major scientific advances in medicine, biology, and neuroscience can be attributed to their use. Despite recent strides in controlling colony diseases and enhancing the environment of captive housed primates, some monkeys develop a syndrome of self injurious behavior (SIB). The occurrence of SIB compromises the goal of promoting psychological well-being as mandated by the Animal Welfare Act (Revised, 1991) and threatens the quality of the monkey research resource. During the previous grant period, we made significant strides in determining the underlying causes of SIB, in identifying factors that trigger episodes of SIB, in explaining why SIB persists, and in evaluating possible treatments. As a result of this effort, we have formulated an integrated developmental neurochemical hypothesis in which SIB arises from adverse life events, is maintained by dysregulations of several neurochemical and physiological systems (e.g., the stress response system and the opioid system), and serves to reduce anxiety. Our goals during this next grant period are to test the generality of this hypothesis, develop screening procedures for identifying precursors to SIB in young primates, explore the influence of various candidate genes in the expression of SIB, and test efficacy of various therapies based directly on our research findings. In our first aim, we will test the hypothesis that SIB is associated with increased behavioral and physiological indices of anxiety. Specific Aim 2 will investigate the relationship between SIB and the endogenous opioid system and determine whether monkeys with SIB exhibit opioid receptor super sensitivity. The third specific aim will focus on a longitudinal prospective study of large cohort of monkeys to identify genetic, behavioral, and physiological markers of SIB. In Specific Aim 4, we will establish effective pharmacological treatments for SIB in monkeys and evaluate individual differences in treatment efficacy.

描述（由申请人提供）： 恒河猴是一种至关重要的研究资源，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并增强了圈养的住房灵长类动物的环境方面，但一些猴子发展了自我伤害行为（SIB）综合征。 SIB的发生损害了促进《动物福利法》（Animal Felfare Act）规定的心理健康的目标（修订，1991年），并威胁了猴子研究资源的质量。在上一个赠款期间，我们在确定SIB的基本原因，确定触发SIB发作的因素，解释SIB持续存在以及评估可能的治疗方面取得了长足的进步。由于这项努力，我们制定了一个综合的发育神经化学假设，其中SIB由不良生活事件引起，由几种神经化学和生理系统的失调（例如，压力响应系统和阿片类药物系统）维持，并减轻焦虑。我们在下一个赠款期间的目标是检验该假设的一般性，制定筛选程序，以识别年轻灵长类动物中的SIB前体，探索各种候选基因在SIB表达中的影响，并直接基于我们的研究发现，测试各种疗法的效率。在我们的第一个目标中，我们将检验以下假设：SIB与焦虑的行为和生理指标增加有关。具体目标2将研究SIB与内源性阿片类药物系统之间的关系，并确定带有SIB的猴子是否表现出阿片类药物受体超级敏感性。第三个具体目标将集中于大型猴子队列的纵向前瞻性研究，以鉴定SIB的遗传，行为和生理标记。在特定的目标4中，我们将在猴子中为SIB建立有效的药理治疗，并评估治疗功效的个体差异。