Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons

Research output: Contribution to journalArticle

Abstract

Background Baclofen, a GABAB receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Methods Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8 mg/kg) or naltrexone (1.0-5.6 mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5 days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. Results When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8 mg/kg) and naltrexone (3.2 and 5.6 mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6 mg/kg), but not baclofen, significantly reduced alcohol seeking. Conclusions Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalDrug and Alcohol Dependence
Volume179
DOIs
StatePublished - Oct 1 2017

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Naltrexone
Baclofen
Self Administration
Papio
Alcohols
Alcohol Abstinence
Therapeutics
Drinking
Reinforcement Schedule
Drug therapy

Keywords

  • Alcohol
  • Baboons
  • Baclofen
  • Naltrexone
  • Seeking
  • Self-administration

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

@article{0c8f2e5999bb4e0d993c4c4df0ff41ce,
title = "Baclofen and naltrexone effects on alcohol self-administration: Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons",
abstract = "Background Baclofen, a GABAB receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Methods Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8 mg/kg) or naltrexone (1.0-5.6 mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5 days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. Results When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8 mg/kg) and naltrexone (3.2 and 5.6 mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6 mg/kg), but not baclofen, significantly reduced alcohol seeking. Conclusions Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection.",
keywords = "Alcohol, Baboons, Baclofen, Naltrexone, Seeking, Self-administration",
author = "August Holtyn and Kaminski, {Barbara J.} and Elise Weerts",
year = "2017",
month = "10",
day = "1",
doi = "10.1016/j.drugalcdep.2017.06.019",
language = "English (US)",
volume = "179",
pages = "47--54",
journal = "Drug and Alcohol Dependence",
issn = "0376-8716",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Baclofen and naltrexone effects on alcohol self-administration

T2 - Comparison of treatment initiated during abstinence or ongoing alcohol access in baboons

AU - Holtyn, August

AU - Kaminski, Barbara J.

AU - Weerts, Elise

PY - 2017/10/1

Y1 - 2017/10/1

N2 - Background Baclofen, a GABAB receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Methods Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8 mg/kg) or naltrexone (1.0-5.6 mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5 days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. Results When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8 mg/kg) and naltrexone (3.2 and 5.6 mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6 mg/kg), but not baclofen, significantly reduced alcohol seeking. Conclusions Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection.

AB - Background Baclofen, a GABAB receptor agonist, is under investigation as a pharmacotherapy for alcohol use disorder. Treatment with a pharmacotherapeutic can be initiated during alcohol abstinence or active drinking, which may influence treatment outcomes. This study examined whether baclofen treatment initiated and maintained during alcohol abstinence would reduce alcohol seeking and self-administration upon return to alcohol access, and whether effects differed from treatment initiated and maintained during ongoing alcohol access. Naltrexone was tested under similar conditions for comparison. Methods Five baboons self-administered alcohol under a three-component chained schedule of reinforcement that modeled periods of anticipation (Component 1), seeking (Component 2), and consumption (Component 3). Alcohol was only available in Component 3. In Experiment 1, baclofen (0.1-1.8 mg/kg) or naltrexone (1.0-5.6 mg/kg) was administered daily beginning on the first day of a 5-day abstinence period and treatment was continued for 5 days of alcohol access. In Experiment 2, selected doses of both drugs were administered during ongoing alcohol access. Results When treatment was initiated during alcohol abstinence, baclofen and naltrexone did not significantly reduce total alcohol intake (g/kg) or alcohol seeking. In comparison, when treatment was initiated during ongoing alcohol access, both baclofen (1.8 mg/kg) and naltrexone (3.2 and 5.6 mg/kg) significantly reduced total alcohol intake (g/kg). Naltrexone (5.6 mg/kg), but not baclofen, significantly reduced alcohol seeking. Conclusions Initiation of baclofen treatment (or other alcohol use disorder treatments) during abstinence or active drinking may be an important factor in influencing efficacy and appropriate dose selection.

KW - Alcohol

KW - Baboons

KW - Baclofen

KW - Naltrexone

KW - Seeking

KW - Self-administration

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U2 - 10.1016/j.drugalcdep.2017.06.019

DO - 10.1016/j.drugalcdep.2017.06.019

M3 - Article

C2 - 28753481

AN - SCOPUS:85025644295

VL - 179

SP - 47

EP - 54

JO - Drug and Alcohol Dependence

JF - Drug and Alcohol Dependence

SN - 0376-8716

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