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A deeper insight into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consumption: lessons learned from a human laboratory investigation.

Study Authors Lorenzo Leggio, Mehdi Farokhnia, Mary Lee and Lisa FarinelliHot Off the Press – January 29, 2019.

The GABA-B receptor agonist baclofen has been investigated and used as a treatment for alcohol use disorder, but data from clinical studies remain inconsistent. Additional research is needed to understand the biobehavioral mechanisms underlying baclofen’s effect in relation to alcohol use. In the present study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in an experiment in a bar-like laboratory. The experimental session consisted of three procedures: alcohol cue-reactivity, priming, and self-administration. Repeated blood samples were also collected for pharmacokinetic measurements. Baclofen, compared to placebo, did not significantly reduce alcohol craving or drinking in aggregate analyses. However, compared to placebo, the link between alcohol priming and self-administration was disrupted under baclofen, suggesting that baclofen may work by uncoupling the link between an initial drink and subsequent alcohol consumption. In addition, considerable inter-individual variability in baclofen pharmacokinetic parameters was observed. Finally, maximum plasma concentrations of baclofen negatively correlated with cue-induced alcohol craving and ratings of alcohol-induced ‘liking more’. These findings provide novel insights into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consummatory behaviors in heavy-drinking alcohol-dependent individuals.

Publication Information

Farokhnia, Mehdi; Deschaine, Sara L; Sadighi, Armin; Farinelli, Lisa A; Lee, Mary R; Akhlaghi, Fatemeh; Leggio, Lorenzo

A deeper insight into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consumption: lessons learned from a human laboratory investigation. Journal Article

In: Mol Psychiatry, 2018, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).

Abstract | Links

@article{Farokhnia:2018aab,
title = {A deeper insight into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consumption: lessons learned from a human laboratory investigation.},
author = {Mehdi Farokhnia and Sara L Deschaine and Armin Sadighi and Lisa A Farinelli and Mary R Lee and Fatemeh Akhlaghi and Lorenzo Leggio},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30382188},
doi = {10.1038/s41380-018-0287-y},
issn = {1476-5578 (Electronic); 1359-4184 (Linking)},
year = {2018},
date = {2018-10-31},
urldate = {2018-10-31},
journal = {Mol Psychiatry},
address = {Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.},
abstract = {Previous studies suggest that GABA-B receptor agonism may represent an effective pharmacological approach to treat addictive disorders. Baclofen is a selective GABA-B receptor agonist which has been investigated as a potential treatment for alcohol use disorder. However, research is needed to understand the biobehavioral mechanisms underlying baclofen's effect on alcohol use. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in a laboratory experiment consisting of three procedures: alcohol cue-reactivity, priming, and self-administration. During the experiment, craving and other subjective responses to alcohol were assessed, and blood samples were collected for pharmacokinetic measurements. The effects of baclofen on the relationships between different alcohol-related laboratory parameters were investigated. Baclofen pharmacokinetic parameters and their correlations with behavioral measures were also examined. Results showed that baclofen disrupted the link between alcohol priming and self-administration, as indicated by significant interaction effects between drug condition (baclofen vs. placebo) and some of the priming variables (alcohol craving: F3},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Previous studies suggest that GABA-B receptor agonism may represent an effective pharmacological approach to treat addictive disorders. Baclofen is a selective GABA-B receptor agonist which has been investigated as a potential treatment for alcohol use disorder. However, research is needed to understand the biobehavioral mechanisms underlying baclofen's effect on alcohol use. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in a laboratory experiment consisting of three procedures: alcohol cue-reactivity, priming, and self-administration. During the experiment, craving and other subjective responses to alcohol were assessed, and blood samples were collected for pharmacokinetic measurements. The effects of baclofen on the relationships between different alcohol-related laboratory parameters were investigated. Baclofen pharmacokinetic parameters and their correlations with behavioral measures were also examined. Results showed that baclofen disrupted the link between alcohol priming and self-administration, as indicated by significant interaction effects between drug condition (baclofen vs. placebo) and some of the priming variables (alcohol craving: F3

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  • https://www.ncbi.nlm.nih.gov/pubmed/30382188
  • doi:10.1038/s41380-018-0287-y

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