Effects of the benzodiazepine GABAA α1-preferring antagonist 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons

- Acute doses of 3-ISOPBC did not decrease alcohol seeking or consumption in baboons.
- Chronic doses of 3-ISOPBC reduced alcohol consumption.
- Chronic doses of 3-ISOPBC did not affect consumption of a non-alcoholic beverage.
- Effects of chronic doses of 3-ISOPBC on consumption were specific to alcohol.

BackgroundThe major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), modulates many of the behavioral effects of alcohol, including sedation, tolerance, and withdrawal. The α1 subunit of the benzodiazepine GABAA receptor is the most widely expressed alpha subunit in the brain, and has been implicated in the reinforcing- and abuse-related effects of alcohol. The aim of the present study was to examine whether treatment with a benzodiazepine GABAA α1-preferring ligand, 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC), selectively decreases alcohol seeking and consumption.MethodsEight baboons self-administered alcohol (4% w/v; n = 5; alcohol group) or a non-alcoholic beverage (n = 3; control group) in Component 3 of a chained schedule of reinforcement. Responses in Component 2 provided indices of motivation to drink (seeking). Doses of 3-ISOPBC (5.0-30.0 mg/kg) and vehicle were administered before drinking sessions under both acute and chronic (5 day) conditions.ResultsChronic, and not acute, administration of 3-ISOPBC significantly decreased self-administration responses, g/kg alcohol consumed, and the number of drinks in and duration of the first drinking bout in the alcohol group. In the control group, chronic administration of 3-ISOPBC did not significantly decrease any of these measures at any of the doses.ConclusionsThe GABAA α1-preferring ligand 3-ISOPBC may have therapeutic potential in the treatment of alcohol use disorder due to its ability to selectively reduce alcohol use.