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

Wake Forest University Health Sciences, Winston-Salem NC

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Abstract

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 ?-endorphin and clarify the receptor mechanisms underlying analgesic effects of CRF and ?-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.