Effects of mu, kappa, and delta opioid receptor agonists on the function of hypothalamic-pituitary-adrenal axis in monkeys

John E. Pascoe, Keith L. Williams, Partha Mukhopadhyay, Kenner C. Rice, James H. Woods, Mei Chuan Ko

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Opioids can modulate neuroendocrine function. Less is known about the involvement of opioid receptor subtypes in the stimulatory effects of opioids on the primate hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the stimulatory effects of opioids selective for each receptor subtype on plasma adrenocorticotropic hormone (ACTH) and cortisol levels in both male and female monkeys. The blood collection procedure was conducted in home-caged and unanesthetized rhesus monkeys that showed low and stable basal ACTH and cortisol levels. Three opioid receptor agonists, fentanyl, U-50488H, and SNC80, were used in behaviorally active doses; they are highly selective for mu, kappa, and delta opioid receptors, respectively. Plasma samples were collected at multiple time points before and after IV administration of each compound and were quantified by radioimmunoassay. Neither fentanyl (0.0003-0.02 mg/kg) nor SNC80 (0.03-0.3 mg/kg) changed either ACTH or cortisol basal levels. In contrast, U-50488H (0.01-1 mg/kg) dose-dependently stimulated ACTH and cortisol release in both male and female monkeys. Importantly, the stimulatory effects of U-50488H on the secretion of ACTH were blocked by a selective kappa opioid receptor antagonist, nor-Binaltorphimine. The antagonist effect of nor-binaltorphimine lasted up to 20 weeks. These results indicate that only synthetic kappa, but not mu or delta opioid receptor agonists stimulate HPA axis activity after acute administration in primates.

Original languageEnglish (US)
Pages (from-to)478-486
Number of pages9
JournalPsychoneuroendocrinology
Volume33
Issue number4
DOIs
StatePublished - May 2008
Externally publishedYes

Keywords

  • ACTH
  • Cortisol
  • HPA axis
  • Opioid receptor agonists
  • Opioid receptor antagonists
  • Primates

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

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