Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Chronic treatment with novel brain-penetrating selective NOP receptor agonist MT-7716 reduces alcohol drinking and seeking in the rat

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Ciccocioppo, R.
  • Stopponi, S.
  • Economidou, D.
  • Kuriyama, M.
  • Kinoshita, H.
  • Heilig, M.
  • Roberto, Marisa
  • Weiss, Friedbert
  • Teshima, K.

publication date

  • October 2014

journal

  • Neuropsychopharmacology  Journal

abstract

  • Since its discovery, the nociceptin/orphanin FQ (N/OFQ)-NOP receptor system has been extensively investigated as a promising target to treat alcoholism. Encouraging results obtained with the endogenous ligand N/OFQ stimulated research towards the development of novel brain-penetrating NOP receptor agonists with a pharmacological and toxicological profile compatible with clinical development. Here we describe the biochemical and alcohol-related behavioral effects of the novel NOP receptor agonist MT-7716. MT-7716 has high affinity for human NOP receptors expressed in HEK293 cells with a Ki value of 0.21 nM. MT-7716 concentration-dependently stimulated GTPγ(35)S binding with an EC50 value of 0.30 nM and its efficacy was similar to N/OFQ, suggesting that MT7716 is a full agonist at NOP receptors. In the two bottle choice test MT-7716 (0, 0.3, 1, and 3 mg/kg, bid) given orally for 14 days dose-dependently decreased voluntary alcohol intake in Marchigian Sardinian rats. The effect became gradually stronger following repeated administration, and was still significant 1 week after discontinuation of the drug. Oral naltrexone (30 mg/kg, bid) for 14 days also reduced ethanol intake; however, the effect decreased over the treatment period and rapidly disappeared when drug treatment was discontinued. MT-7716 is also effective for preventing reinstatement caused by both ethanol-associated environmental stimuli and stress. Finally, to investigate the effect of MT-7716 on alcohol withdrawal symptoms, Wistar rats were withdrawn from a 7-day alcohol liquid diet. MT-7716 significantly attenuated somatic alcohol withdrawal symptoms. Together these findings indicate that MT-7716 is a promising candidate for alcoholism treatment remaining effective with chronic administration.

subject areas

  • Acenaphthenes
  • Alcohol Deterrents
  • Alcohol Drinking
  • Animals
  • Benzimidazoles
  • Choice Behavior
  • Dose-Response Relationship, Drug
  • Drug-Seeking Behavior
  • HEK293 Cells
  • Humans
  • Male
  • Naltrexone
  • Narcotic Antagonists
  • Opioid Peptides
  • Rats
  • Rats, Wistar
  • Receptors, Opioid
  • Stress, Psychological
  • Substance Withdrawal Syndrome
scroll to property group menus

Identity

PubMed Central ID

  • PMC4207340

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/npp.2014.113

PubMed ID

  • 24863033
scroll to property group menus

Additional Document Info

start page

  • 2601

end page

  • 2610

volume

  • 39

issue

  • 11

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support