Nature Neuroscience 8, 1735 - 1741 (2005)
Published online: 20 November 2005; | doi:10.1038/nn1585
The prolactin-releasing peptide antagonizes the opioid system through its receptor GPR10Patrick Laurent1, 4, Jerome A J Becker1, 4, Olga Valverde2, Catherine Ledent1, Alban de Kerchove d'Exaerde3, Serge N Schiffmann3, Rafael Maldonado2, Gilbert Vassart1
& Marc Parmentier11
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. 2
Laboratori de Neurofarmacologia, Facultat de Ciènces de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain. 3
Laboratory of Neurophysiology, Université Libre de Bruxelles, Campus Erasme, Route de Lennik 808, Brussels, Belgium. 4
These authors contributed equally to this work.
Correspondence should be addressed to Marc Parmentier mparment@ulb.ac.be 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.
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