title: Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats.
abstract: BACKGROUND
  Previous findings have shown that intra-accumbens injection of naltrexone, a non-selective opioid antagonist, blocks the acquisition of rapid tolerance to ethanol in rats. This study investigates the effects of intra-accumbens injection of the selective mu-, delta-, and kappa-opioid antagonists, respectively, naloxonazine, naltrindole, and nor-binaltorphimine, on rapid tolerance to ethanol.
  
  
  METHODS
  Male Wistar rats with guide cannulae directed to the shell or the core portions of the nucleus accumbens received a microinjection of naloxonazine (2-4 microg), naltrindole (2-4 microg), nor-binaltorphimine (2.5-5 microg), or vehicle. After 5 min, each group was divided in two groups that received ethanol (2.7 g/kg i.p.) or saline. Rats were then tested for motor coordination on the tilting plane apparatus. Twenty four hours later, all rats received a challenge dose of ethanol (2.7 g/kg i.p.) and were tested on the tilt plane again.
  
  
  RESULTS
  Repeated injections of ethanol caused a reduction in motor impairment suggesting the development of tolerance. However, rats injected with 4 microg naloxonazine into either core or shell portions of the nucleus accumbens did not exhibit tolerance when challenged with ethanol on day 2. Rats treated with 5 microg nor-binaltorphimine into accumbens core plus intraperitoneal saline on day 1 showed reduced motor impairment when challenged with ethanol on day 2, suggesting cross-tolerance to ethanol.
  
  
  CONCLUSIONS
  Taken together, our results suggests that mu-opioid receptors in both shell and core portions of the nucleus accumbens, and possibly kappa-opioid in the core, participate in the modulation of rapid tolerance to ethanol.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, CCB, Universidade Federal de Santa Catarina, Campus Universitário Trindade, 88049-900, Florianópolis, Santa Catarina, Brazil. RVaraschin@salud.unm.edu
authors.forename: Rafael Koerich
authors.initials: RK
authors.lastname: Varaschin
authors.forename: Gina Struffaldi
authors.initials: GS
authors.lastname: Morato
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*
chemical_list: D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D000431:Ethanol; D009271:Naltrexone; C034643:naloxonazine; C055382:naltrindole