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

促肾上腺皮质激素释放因子(CRF)被认为是个体的关键介质 对压力做出反应。然而，关于中央银行的影响的报道很少。 灵长类动物的慢性肾功能衰竭。我们建议研究脑池内注射CRF的效果。 在成年恒河猴中，通过使用不同的行为和 生理化验。特别是，这些猴子的化验是专门建立的 为了反映调节疼痛和瘙痒的感觉过程，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 (类抑郁和类焦虑行为)反应。在这项提案的第一个目标中，我们将 建立中枢性促肾上腺皮质激素释放激素与β-内啡肽的不同止痛谱并阐明其受体 促肾上腺皮质激素释放激素和β-内啡肽的镇痛作用机制。在第二个目标中， 将进行几项分析，以提供广泛的神经内分泌、自主神经、 中枢性CRF在猴子体内引起的行为反应。我们独特的一套生理学 以及在清醒的、行为正常的恒河猴体内植入导管的行为分析 脑池内注射神经肽，与受体选择性拮抗剂相结合， 将为中枢CRF调节多种生理功能提供有价值的功能证据 功能和提高我们对参与应激诱导的神经肽的理解 灵长类动物的止痛药。

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.