Abstract
BACKGROUND: Preclinical studies in rodents have demonstrated inhibitory effects of glucagon-like peptide-1 (GLP-1) receptor stimulation on alcohol consumption. The effects of GLP-1 receptor stimulation on alcohol intake in primates have not been investigated.
METHODS: We performed placebo-controlled studies on the effects of the GLP-1 receptor agonists exenatide and liraglutide on alcohol consumption in alcohol-preferring male African vervet monkeys. Monkeys selected for voluntary alcohol drinking were observed for at least 10 days of baseline drinking and allocated to drug or vehicle (n = 11-12 per group) balanced with respect to alcohol intake. Monkeys had access to alcohol 4 h/day. In a first study, monkeys were treated with exenatide 0.04 mg/kg or vehicle once weekly for 5 weeks to obtain steady-state plasma levels. In a second study, monkeys were treated daily with liraglutide (increasing dosing, 10 to 50 μg/kg/day) or vehicle over 2 weeks. In both studies, access to alcohol was suspended during drug up-titration. Then, alcohol was again made available 4 h/day and treatment was continued for 2 weeks, during which alcohol intake was recorded. Observation of alcohol intake was continued for a week of drug washout.
RESULTS: Liraglutide and to a lesser extent exenatide significantly reduced alcohol consumption without causing any signs of emesis and with no effect on water intake as compared to vehicle.
CONCLUSIONS: The present study demonstrates for the first time that GLP-1 receptor agonists can reduce voluntary alcohol drinking in non-human primates. The data substantiate the potential usefulness of GLP-1 receptor agonists in the treatment of alcohol use disorder.
| Original language | English |
|---|---|
| Journal | Psychopharmacology |
| Volume | 236 |
| Issue number | 2 |
| Pages (from-to) | 603–611 |
| ISSN | 0033-3158 |
| DOIs | |
| Publication status | Published - 14 Feb 2019 |
Keywords
- Alcohol use disorder
- Exendin-4
- GLP-1
- Liraglutide
- Non-human primate
- Pharmacotherapy
