The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10.
Prolactin-releasing peptide (PrRP) and its receptor G protein-coupled receptor 10 (GPR10) are expressed in brain areas involved in the processing of nociceptive signals. We investigated the role of this new neuropeptidergic system in GPR10-knockout mice. These mice had higher nociceptive thresholds and stronger stress-induced analgesia than wild-type mice, differences that were suppressed by naloxone treatment. In addition, potentiation of morphine-induced antinociception and reduction of morphine tolerance were observed in mutants. Intracerebroventricular administration of PrRP in wild-type mice promoted hyperalgesia and reversed morphine-induced antinociception. PrRP administration had no effect on GPR10-mutant mice, showing that its effects are mediated by GPR10. Anti-opioid effects of neuropeptide FF were found to require a functional PrRP-GPR10 system. Finally, GPR10 deficiency enhanced the acquisition of morphine-induced conditioned place preference and decreased the severity of naloxone-precipitated morphine withdrawal syndrome. Altogether, our data identify the PrRP-GPR10 system as a new and potent negative modulator of the opioid system.
Laurent
Patrick
P
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Campus Erasme, Route de Lennik 808, Brussels, Belgium.
Becker
Jerome A J
JA
Valverde
Olga
O
Ledent
Catherine
C
de Kerchove d'Exaerde
Alban
A
Schiffmann
Serge N
SN
Maldonado
Rafael
R
Vassart
Gilbert
G
Parmentier
Marc
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004357:Drug Synergism; D004361:Drug Tolerance / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007028:Hypothalamic Hormones / Q000378:metabolism* / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000819:agonists; D009292:Narcotic Antagonists / Q000494:pharmacology; D009434:Neural Pathways / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D056690:Prolactin-Releasing Hormone; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D007028:Hypothalamic Hormones; D009292:Narcotic Antagonists; D009479:Neuropeptides; D018847:Opioid Peptides; C534378:Prlh protein, mouse; C487625:Prlhr protein, mouse; D056690:Prolactin-Releasing Hormone; D043562:Receptors, G-Protein-Coupled; D009020:Morphine