Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain / drug effects
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Brain / metabolism*
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Conditioning, Psychological / drug effects
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Conditioning, Psychological / physiology
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Disease Models, Animal
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Drug Synergism
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Drug Tolerance / physiology
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Hyperalgesia / chemically induced
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Hyperalgesia / metabolism
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Hyperalgesia / physiopathology
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Hypothalamic Hormones / metabolism*
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Hypothalamic Hormones / pharmacology
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Injections, Intraventricular
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Mice
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Mice, Knockout
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Morphine / agonists
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Narcotic Antagonists / pharmacology
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Neural Pathways / metabolism*
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Neuropeptides / metabolism*
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Neuropeptides / pharmacology
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Opioid Peptides / metabolism*
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Pain / chemically induced
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Pain / metabolism*
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Pain / physiopathology
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Pain Threshold / drug effects
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Pain Threshold / physiology
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Prolactin-Releasing Hormone
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / physiology*
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Substance Withdrawal Syndrome / genetics
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Substance Withdrawal Syndrome / metabolism
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Substance Withdrawal Syndrome / physiopathology
Substances
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Hypothalamic Hormones
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Narcotic Antagonists
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Neuropeptides
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Opioid Peptides
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Prlh protein, mouse
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Prlhr protein, mouse
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Prolactin-Releasing Hormone
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Receptors, G-Protein-Coupled
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Morphine