title: Systemic κ-opioid receptor antagonism by nor-binaltorphimine reduces dependence-induced excessive alcohol self-administration in rats.
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.
authors.affiliation: The Scripps Research Institute, La Jolla, CA, USA. b_walker@wsu.edu
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Walker
authors.forename: Eric P
authors.initials: EP
authors.lastname: Zorrilla
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000280:Administration, Inhalation; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000502:physiology; D000431:Ethanol / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors* / Q000502:physiology; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D000431:Ethanol; D009271:Naltrexone; D004399:Dynorphins