Systemic κ-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats

Addict Biol. 2011 Jan;16(1):116-9. doi: 10.1111/j.1369-1600.2010.00226.x.

Abstract

Altered dynorphin opioid peptide systems contribute to increased ethanol self-administration during withdrawal following chronic alcohol exposure. We previously identified that the κ-opioid receptor antagonist nor-binaltorphimine (nor-BNI) selectively reduced ethanol self-administration in dependent animals. The purpose of this study was twofold: (1) determine whether peripherally administered nor-BNI could reduce dependence-induced ethanol self-administration and (2) confirm the selective κ-opioid effects of nor-BNI by administering it 24 hours prior to ethanol self-administration sessions occurring during acute withdrawal. Nor-BNI decreased ethanol self-administration in ethanol-dependent animals, with no effect in nondependent animals. Thus, the κ-opioid/dynorphin system is a viable pharmacotherapeutic target for the treatment of alcoholism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Alcohol Deterrents / pharmacology*
  • Alcoholism / physiopathology*
  • Animals
  • Dose-Response Relationship, Drug
  • Dynorphins / physiology
  • Ethanol / toxicity
  • Injections, Subcutaneous
  • Male
  • Naltrexone / analogs & derivatives*
  • Naltrexone / pharmacology
  • Narcotic Antagonists / pharmacology*
  • Premedication
  • Rats
  • Rats, Wistar
  • Receptors, Opioid, kappa / antagonists & inhibitors*
  • Receptors, Opioid, kappa / physiology
  • Self Administration
  • Substance Withdrawal Syndrome / physiopathology

Substances

  • Alcohol Deterrents
  • Narcotic Antagonists
  • Receptors, Opioid, kappa
  • norbinaltorphimine
  • Ethanol
  • Naltrexone
  • Dynorphins