Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats.
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.
Varaschin
Rafael Koerich
RK
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
Morato
Gina Struffaldi
GS
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*
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D000431:Ethanol; D009271:Naltrexone; C034643:naloxonazine; C055382:naltrindole