title: Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice.
abstract: BACKGROUND
  Several studies implicate stress as a risk factor for the development and maintenance of drug addictive behaviors and drug relapse. Kappa opioid receptor (KOR) antagonists have been shown to attenuate behavioral responses to stress and stress-induced reinstatement of cocaine and ethanol seeking and preference.
  
  
  OBJECTIVE
  In the current study, we determined whether the selective KOR antagonist, norbinaltorphimine (nor-BNI), would block stress-induced reinstatement of nicotine preference.
  
  
  METHODS
  Adult Institute of Cancer Research mice were conditioned with 0.5 mg/kg nicotine, injected subcutaneously (s.c.) for 3 days and tested in the nicotine-conditioned place preference (CPP) model. After 3 days extinction, nor-BNI (10 mg/kg, s.c.) was administered 16 h prior to a priming dose of nicotine (0.1 mg/kg, s.c.), and mice were tested in the CPP model for nicotine-induced reinstatement of CPP. A separate group of mice was subjected to a 2-day modified forced swim test (FST) paradigm to induce stress after 3 days extinction from CPP. Mice were given vehicle or nor-BNI (10 mg/kg, s.c.) 16 h prior to each FST session.
  
  
  RESULTS
  Nor-BNI pretreatment significantly attenuated stress-induced reinstatement of nicotine-CPP, but had no effect on nicotine-primed reinstatement.
  
  
  CONCLUSIONS
  Blockade of KORs by selective antagonists attenuates stress-induced reinstatement of nicotine-CPP. Overall, the kappa opioid system may serve as a therapeutic target for suppressing multiple signaling processes which contribute to maintenance of smoking, smoking relapse, and drug abuse in general.
authors.affiliation: Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23219, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Jackson
authors.forename: J P
authors.initials: JP
authors.lastname: McLaughlin
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
authors.forename: M I
authors.initials: MI
authors.lastname: Damaj
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D005108:Extinction, Psychological; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D012008:Recurrence; D012307:Risk Factors; D012646:Self Administration; D012907:Smoking / Q000453:epidemiology; D013315:Stress, Psychological / Q000523:psychology*
chemical_list: D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D009538:Nicotine