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

Article Details

Citation

Copy to clipboard

Pascoe JE, Williams KL, Mukhopadhyay P, Rice KC, Woods JH, Ko MC

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

Psychoneuroendocrinology. 2008 May;33(4):478-86. doi: 10.1016/j.psyneuen.2008.01.006. Epub 2008 Mar 5.

PubMed ID

18325678 [ View in PubMed

]

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 (0.0003-0.02mg/kg) nor SNC80 (0.03-0.3mg/kg) changed either ACTH or cortisol basal levels. In contrast, U-50488H (0.01-1mg/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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
3-Methylthiofentanyl	Kappa-type opioid receptor	Protein	Humans	Yes	Agonist	Details
Fentanyl	Kappa-type opioid receptor	Protein	Humans	Unknown	Agonist	Details
Remifentanil	Kappa-type opioid receptor	Protein	Humans	Unknown	Agonist	Details