Role of Nociceptin/Orphanin FQ and NOP Receptors in the Response to Acute and Repeated Restraint Stress in Rats

Central nociceptin/orphanin FQ (N/OFQ)‐expressing neurones are abundantly expressed in the hypothalamus and limbic system and are implicated in the regulation of activity of the hypothalamic‐pituitary‐adrenal axis (HPA) and stress responses. We investigated the role of the endogenous N/OFQ receptor...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neuroendocrinology 2012-12, Vol.24 (12), p.1527-1541
Main Authors: Delaney, G., Dawe, K. L., Hogan, R., Hunjan, T., Roper, J., Hazell, G., Lolait, S. J., Fulford, A. J.
Format: Article
Language:English
Subjects:
ACTH
Acute Disease
Aminoquinolines - pharmacology
Amygdala
Animals
bed nucleus
Benzamides - pharmacology
Biological and medical sciences
Brain
Chronic Disease
Corticosterone
Forebrain
Fos protein
Fundamental and applied biological sciences. Psychology
glucocorticoids cortisol/corticosterone
Hippocampus
Hypothalamic-pituitary-adrenal axis
Hypothalamo-Hypophyseal System - drug effects
Hypothalamo-Hypophyseal System - metabolism
Limbic system
Male
mRNA expression
Narcotic Antagonists
neuropeptides
Nociceptin
Nociceptin Receptor
Original
Paraventricular nucleus
Pituitary-Adrenal System - drug effects
Pituitary-Adrenal System - metabolism
Polymerase chain reaction
Rats
Rats, Sprague-Dawley
Receptor mechanisms
Receptors, Opioid - genetics
Receptors, Opioid - metabolism
Receptors, Opioid - physiology
Recurrence
restraint
Restraint, Physical - physiology
Restraint, Physical - psychology
Stress
Stress, Psychological - genetics
Stress, Psychological - metabolism
Thalamus
Time Factors
Vertebrates: endocrinology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Central nociceptin/orphanin FQ (N/OFQ)‐expressing neurones are abundantly expressed in the hypothalamus and limbic system and are implicated in the regulation of activity of the hypothalamic‐pituitary‐adrenal axis (HPA) and stress responses. We investigated the role of the endogenous N/OFQ receptor (NOP) system using the nonpeptidic NOP antagonist, JTC‐801 [N‐(4‐amino‐2‐methylquinolin‐6‐yl)‐2‐(4‐ethylphenoxy‐methyl)benzamide monohydrochloride], during the HPA axis response to acute physical/psychological stress (60 min of restraint). Although i.v. JTC‐801 (0.05 mg/kg in 100 μl) had no significant effect on restraint‐induced plasma corticosterone release at 30 or 60 min post‐injection, i.v. JTC‐801 (0.05 mg/kg in 100 μl) in quiescent rats significantly increased basal plasma corticosterone at the 30‐min time‐point compared to i.v. vehicle (1% dimethysulphoxide in sterile saline). Central injection of JTC‐801 i.c.v. was associated with increased Fos expression in the parvocellular paraventricular nucleus 90 min after infusion compared to vehicle control. These findings contrast to the effects of i.c.v. UFP‐101, a NOP antagonist that we have previously shown to have no effect on HPA activity in quiescent rats. To determine whether restraint stress was associated with compensatory changes in N/OFQ precursor (ppN/OFQ) or NOP receptor mRNAs, in a separate study, we undertook reverse transcriptase‐polymerase chain reaction and in situ hybridisation analysis of ppN/OFQ and NOP transcripts in the brains of male Sprague–Dawley rats. In support of an endogenous role for central N/OFQ in psychological stress, we found that acute restraint significantly decreased preproN/OFQ transcript expression in the hippocampus 2 h after stress compared to unstressed controls. PpN/OFQ mRNA was also reduced in the mediodorsal forebrain 4 h after stress. NOP mRNA was reduced in the hypothalamus 2 h after restraint and at 4 h in mediodorsal forebrain and hippocampus. In situ hybridisation analysis showed that acute restraint significantly decreased ppNN/OFQ in the central amygdala, with significantly increased expression in bed nucleus and reticular thalamus associated with repeated restraint. There was a strong trend for reduced NOP mRNA in the bed nucleus of acute and repeated restraint groups, although there were no other significant changes seen. Although the exact mechanisms require elucidation, the findings obtained in the present study provide evidence indicating that the endog
ISSN:0953-8194
1365-2826
DOI:10.1111/j.1365-2826.2012.02361.x