Diverse Effects of a Stress-Related Ligand, Corticotropin-Releasing Factor, in Non-Human Primates

压力相关配体促肾上腺皮质激素释放因子对非人类灵长类动物的多种影响

• 批准号: 9751235
• 负责人: MEI-CHUAN KO
• 金额: $ 19.38万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751235
• 关键词: Absence of pain sensation; Acute; Adult; Affinity; Analgesics; Animals; Anxiety; Attention; Behavior; Behavioral; Behavioral Assay; Biological; Biological Assay; Blood Pressure; Body Temperature; Brain region; Capsaicin; Cardiovascular system; Carrageenan; Catheters; Characteristics; Comorbidity; Corticotropin; Corticotropin-Releasing Hormone; Coupled; Data; Dose; Effectiveness; Electrocardiogram; Evaluation; Foundations; GTP-Binding Proteins; Heart Rate; Hormonal; Human; Hydrocortisone; Hyperalgesia; Implant; Individual; Knowledge; Ligands; Macaca mulatta; Mediating; Mediator of activation protein; Mental Depression; Modality; Monkeys; Mood Disorders; Neuropeptides; Neurosecretory Systems; Nociception; Opioid Antagonist; Pain; Pharmaceutical Preparations; Pharmacology Study; Phylogenetic Analysis; Physiological; Physiology; Plasma; Primates; Pruritus; Public Health; Reporting; Research; Respiration; Respiratory physiology; Rodent; Role; Sensory; Signal Transduction; Site; Stress; System; Testing; allodynia; anxiety-like behavior; awake; base; behavioral response; beta-Endorphin; depressive symptoms; hypothalamic-pituitary-adrenal axis; improved; mu opioid receptors; nonhuman primate; pain processing; paraventricular nucleus; receptor; receptor function; response; stressor; temporal measurement; urinary

Corticotropin-releasing factor (CRF) is considered as a key mediator for individuals responding to stress. However, there have been very few reports on the effects of central CRF in primates. We propose to investigate the effects of intracisternally administered CRF in adult rhesus monkeys over a wide dose range by using diverse behavioral and physiological assays. In particular, these monkey assays have been established specifically to reflect the sensory processing for regulating pain and itch, neuroendocrine (ACTH and cortisol release), autonomic (respiration and cardiovascular activities), and behavioral (depressive-like and anxiety-like behavior) responses. In the first aim of this proposal, we will establish distinct analgeic profiles of central CRF versus β-endorphin and clarify the receptor mechanisms underlying analgesic effects of CRF and β-endorphin. In the second aim, several assays will be conducted to provide a broad repertoire of neuroendocrine, autonomic, and behavioral responses elicited by central CRF in monkeys. Our unique set of physiological and behavioral assays in awake, behaving rhesus monkeys implanted with catheters for intracisternal delivery of neuropeptides, in combination with receptor-selective antagonists, will provide valuable functional evidence of central CRF for modulating diverse physiological functions and improve our understanding of neuropeptides involved in stress-induced analgesia in primates.

促肾上腺皮质激素释放因子（CRF）被认为是一个关键的调解人， 对压力的反应然而，关于中央集权的影响的报道很少。 灵长类动物的CRF。我们建议研究脑池内给药CRF的作用 在成年恒河猴中，通过使用不同的行为和 生理测定特别是，这些猴试验已专门建立， 为了反映调节疼痛和瘙痒的感觉处理，神经内分泌（ACTH和 皮质醇释放）、自主神经（呼吸和心血管活动）和行为 （抑郁样和焦虑样行为）反应。在本建议的第一个目标中，我们将 建立中枢CRF与β-内啡肽的不同代谢谱，并阐明受体 CRF和β-内啡肽镇痛作用的机制。第二个目标， 将进行几种测定以提供神经内分泌，自主， 以及中枢CRF引起的猴行为反应。我们独特的一套生理 以及在清醒的、行为正常的恒河猴中进行的行为测定， 脑池内递送神经肽，与受体选择性拮抗剂组合， 为中枢CRF调节多种生理功能提供了有价值的功能证据 功能和提高我们对参与应激诱导的神经肽的理解 灵长类动物的镇痛