Literature DB >> 17207100

Development of naltrexone supersensitivity during food-maintained responding enhances naltrexone's ability to reduce ethanol-maintained responding.

Keith L Williams1.   

Abstract

BACKGROUND: Similar doses of the opiate antagonist naltrexone (NTX) reduce responding maintained by food and ethanol. In animals responding for food, repeated administration of NTX produces supersensitivity to NTX. The purpose of this study was to determine whether the factors that produce enhanced sensitivity to NTX during food-maintained responding also contribute to NTX's ability to reduce ethanol-maintained responding.
METHODS: Rats (n=12) were trained to lever press using food reinforcement. After responding stabilized, the rats were trained to respond for 10% ethanol. Before ethanol sessions, injections of 30 mg/kg NTX were given. Subsequently, weekly cumulative NTX dose-effect curves (1, 3, 10, 30, and 100 mg/kg), known to produce NTX supersensitivity, were determined during food-maintained responding in half the rats for 8 weeks while the other half of the rats received saline vehicle injections instead. To determine whether NTX supersensitivity would transfer to ethanol self-administration, ethanol-maintained responding was re-established and 30 mg/kg NTX was administered again.
RESULTS: Initially, 30 mg/kg NTX had little effect on ethanol-maintained responding. During food-maintained responding, supersensitivity developed in rats receiving weekly cumulative NTX injections. After development of supersensitivity, 30 mg/kg decreased ethanol-maintained responding. Naltrexone's potency to reduce ethanol-maintained responding was unchanged in rats that received only vehicle injections for 8 weeks.
CONCLUSION: The mechanisms that produce NTX supersensitivity during food-maintained responding may play a role in NTX's effect on ethanol consumption. Naltrexone's effect on responding for ethanol was much smaller than that reported in other studies. Further exploration may lead to techniques that maximize NTX's effect on ethanol while minimizing its effect on other behaviors.

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Year:  2007        PMID: 17207100     DOI: 10.1111/j.1530-0277.2006.00272.x

Source DB:  PubMed          Journal:  Alcohol Clin Exp Res        ISSN: 0145-6008            Impact factor:   3.455


  5 in total

1.  Comparison of dehydroepiandrosterone (DHEA) and pregnanolone with existing pharmacotherapies for alcohol abuse on ethanol- and food-maintained responding in male rats.

Authors:  Mary W Hulin; Michelle N Lawrence; Russell J Amato; Peter F Weed; Peter J Winsauer
Journal:  Alcohol       Date:  2015-01-06       Impact factor: 2.405

2.  Effects of CRF1-receptor and opioid-receptor antagonists on dependence-induced increases in alcohol drinking by alcohol-preferring (P) rats.

Authors:  Nicholas W Gilpin; Heather N Richardson; George F Koob
Journal:  Alcohol Clin Exp Res       Date:  2008-07-10       Impact factor: 3.455

3.  Effect of naltrexone during extinction of alcohol-reinforced responding and during repeated cue-conditioned reinstatement sessions in a cue exposure style treatment.

Authors:  Keith L Williams; Jasmine S Schimmel
Journal:  Alcohol       Date:  2008-09-06       Impact factor: 2.405

4.  Drug effects on multiple and concurrent schedules of ethanol- and food-maintained behaviour: context-dependent selectivity.

Authors:  B C Ginsburg; R J Lamb
Journal:  Br J Pharmacol       Date:  2014-07       Impact factor: 8.739

5.  Potency of naltrexone to reduce ethanol self-administration in rats is greater for subcutaneous versus intraperitoneal injection.

Authors:  Keith L Williams; Carissa L Broadbridge
Journal:  Alcohol       Date:  2009-03       Impact factor: 2.405

  5 in total

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