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Effect of novel nociceptin/orphanin FQ-NOP receptor ligands on ethanol drinking in alcohol-preferring msP rats

Academic Article
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Overview

authors

  • Economidou, D.
  • Fedeli, A.
  • Martin-Fardon, Remi
  • Weiss, Friedbert
  • Massi, M.
  • Ciccocioppo, R.

publication date

  • December 2006

journal

  • Peptides  Journal

abstract

  • Activation of the NOP receptor by the endogenous ligand nociceptin/orphanin FQ (N/OFQ) reduces alcohol consumption in genetically selected alcohol-preferring Marchigian Sardinian (msP) rats. The present study evaluated the effect of three newly synthesized peptidergic and one brain-penetrating heterocyclic NOP receptor agonists on alcohol drinking in the two bottle choice paradigm. MsP rats were intracerebroventricularly (ICV) injected with the NOP receptor agonists OS-462 (0.5 and 1.0 microg), UFP-102 (0.25 and 1.0 microg) or UFP-112 (0.01 and 0.05 microg), or with Ro 64-6198 (0.3 and 1.0 mg/kg) given intraperitoneally (i.p.) and tested for 10% alcohol consumption. Results showed decreased alcohol consumption after treatment with all three peptidergic NOP receptor agonists (OS-462, UFP-102 and UFP-112). OS-462 (at the 1.0 microg dose) and UFP-102 (at the 0.25 microg dose) induced a significant increase in food intake as well. Surprisingly, Ro 64-6198 was ineffective at the 0.3 mg/kg dose, whereas it increased ethanol and food consumption at the 1.0 mg/kg dose. Pre-treatment with the selective mu-receptor antagonist naloxone (0.5 mg/kg, i.p.) reduced these effects of 1.0 mg/kg of Ro 64-6198. These findings confirm that activation of brain NOP receptors reduces alcohol drinking in msP rats and demonstrate that OS-462, UFP-102 and UFP-112 act as potent NOP receptor agonists. On the other hand, Ro 64-6198 increased alcohol drinking, an effect probably induced by a residual agonist activity of this compound at mu-opioid receptors. Overall, the results indicate that OS-462, UFP-102 and UFP-112 may represent valuable pharmacological tools to investigate the functional role of the brain N/OFQ system.

subject areas

  • Alcohol Drinking
  • Animals
  • Imidazoles
  • Ligands
  • Male
  • Opioid Peptides
  • Rats
  • Spiro Compounds
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Research

keywords

  • NOP receptor
  • alcohol intake
  • nociceptin/orphanin FQ
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Identity

PubMed Central ID

  • PMC1847604

International Standard Serial Number (ISSN)

  • 0196-9781

Digital Object Identifier (DOI)

  • 10.1016/j.peptides.2006.09.007

PubMed ID

  • 17097763
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Additional Document Info

start page

  • 3299

end page

  • 3306

volume

  • 27

issue

  • 12

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