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.

Effects of glucagon-like peptide 1 analogs on alcohol intake in alcohol-preferring vervet monkeys

“…Other limitations of the study include relatively short study duration, a lack of positive control e.g., naltrexone, and the inclusion of only male monkeys. In baboons, naltrexone reduced drinking to a degree comparable to our liraglutide effect (Holtyn et al 2017). Finally, both this study and our previous mouse study ( Thomsen et al 2017) tested (sub)chronic GLP-1 receptor agonist administration initiated under conditions of suspended alcohol access (which may reflects aspects relevant to relapse in humans).…”

Suppressing Effect of Baclofen on Multiple Alcohol-Related Behaviors in Laboratory Animals

“…Two recent studies ( 49 , 50 ) investigated the effect of baclofen on alcohol self-administration in non-human primates. In both studies, adult male baboons were exposed to a chained schedule of reinforcement with three linked components; sequential completion of RR of each component made alcohol available.…”

“…Treatment with baclofen decreased lever-responding for alcohol, number of alcohol drinks, and amount of self-administered alcohol. Treatment with baclofen was effective when initiated during ongoing alcohol access, but not when initiated during an alcohol-abstinence period preceding alcohol access ( 50 ). These data are in agreement with the results of human studies indicating a greater efficacy of baclofen when treatment was initiated during active drinking [e.g., ( 51 )] rather than after abstinence had been achieved [e.g., ( 52 )].…”

Evaluation of mifepristone effects on alcohol-seeking and self-administration in baboons.

“…We have also demonstrated that seeking and self-administration behaviors associated with alcohol were augmented after abstinence (Weerts et al, 2006), and alcohol-maintained behaviors were more resistant to extinction when compared with behaviors maintained by a preferred, nonalcoholic beverage (Holtyn et al, 2014). In addition, alcohol-seeking and self-administration were reduced by administration of naltrexone, baclofen, and varenicline (Duke, Kaminski, & Weerts, 2014; Holtyn, Kaminski, & Weerts, 2017; Kaminski, Duke, & Weerts, 2012; Kaminski & Weerts, 2014).…”