Next Article in Journal
Towards a Better Understanding of GABAergic Remodeling in Alzheimer’s Disease
Next Article in Special Issue
Association between Stress and the HPA Axis in the Atopic Dermatitis
Previous Article in Journal
Protocatechuic Acid from Pear Inhibits Melanogenesis in Melanoma Cells
Previous Article in Special Issue
Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(8), 1810; doi:10.3390/ijms18081810

NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents

1
Graduate Institute of Biomedical Sciences, Department of Physiology and Pharmacology, Chang Gung University, No. 259 Wenhwa 1st Road, Guishan, Taoyuan 333, Taiwan
2
Department of Biomedical Sciences, Chang Gung University, Taoyuan 333, Taiwan
3
Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan
4
Neuroscience Research Center, Chang Gung Memorial Hospital, No. 5, Fusing St., Guishan, Taoyuan 333, Taiwan
5
Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
*
Author to whom correspondence should be addressed.
Received: 9 June 2017 / Revised: 16 August 2017 / Accepted: 18 August 2017 / Published: 21 August 2017
View Full-Text   |   Download PDF [1673 KB, uploaded 21 August 2017]   |  

Abstract

Neuropeptide FF (NPFF) belongs to the RFamide family and is known as a morphine-modulating peptide. NPFF regulates various hypothalamic functions through two receptors, NPFFR1 and NPFFR2. The hypothalamic-pituitary-adrenal (HPA) axis participates in physiological stress response by increasing circulating glucocorticoid levels and modulating emotional responses. Other RFamide peptides, including neuropeptide AF, neuropeptide SF and RFamide related peptide also target NPFFR1 or NPFFR2, and have been reported to activate the HPA axis and induce anxiety- or depression-like behaviors. However, little is known about the action of NPFF on HPA axis activity and anxiety-like behaviors, and the role of the individual receptors remains unclear. In this study, NPFFR2 agonists were used to examine the role of NPFFR2 in activating the HPA axis in rodents. Administration of NPFFR2 agonists, dNPA (intracerebroventricular, ICV) and AC-263093 (intraperitoneal, IP), time-dependently (in rats) and dose-dependently (in mice) increased serum corticosteroid levels and the effects were counteracted by the NPFF receptor antagonist, RF9 (ICV), as well as corticotropin-releasing factor (CRF) antagonist, α-helical CRF(9-41) (intravenous, IV). Treatment with NPFFR2 agonist (AC-263093, IP) increased c-Fos protein expression in the hypothalamic paraventricular nucleus and induced an anxiogenic effect, which was evaluated in mice using an elevated plus maze. These findings reveal, for the first time, that the direct action of hypothalamic NPFFR2 stimulates the HPA axis and triggers anxiety-like behaviors. View Full-Text
Keywords: neuropeptide FF (NPFF); NPFFR2; HPA axis; anxiety; PVN; CRF neuropeptide FF (NPFF); NPFFR2; HPA axis; anxiety; PVN; CRF
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lin, Y.-T.; Yu, Y.-L.; Hong, W.-C.; Yeh, T.-S.; Chen, T.-C.; Chen, J.-C. NPFFR2 Activates the HPA Axis and Induces Anxiogenic Effects in Rodents. Int. J. Mol. Sci. 2017, 18, 1810.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top