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Effects of the benzodiazepine GABAA α1-preferring antagonist 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons. Drug Alcohol Depend 2017 Jan 01;170:25-31

Date

11/20/2016

Pubmed ID

27865151

Pubmed Central ID

PMC5183547

DOI

10.1016/j.drugalcdep.2016.10.036

Scopus ID

2-s2.0-84995700083   6 Citations

Abstract

BACKGROUND: The 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.

METHODS: Eight 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 (5.0-30.0mg/kg) and vehicle were administered before drinking sessions under both acute and chronic (5day) conditions.

RESULTS: Chronic, 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.

CONCLUSIONS: The 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.

Author List

Holtyn AF, Tiruveedhula VV, Stephen MR, Cook JM, Weerts EM

Author

James M. Cook PhD University Distinguished Professor in the Chemistry and Biochemistry department at University of Wisconsin - Milwaukee




MESH terms used to index this publication - Major topics in bold

Alcohol Drinking
Animals
Benzodiazepines
Drug-Seeking Behavior
Ethanol
GABA-A Receptor Antagonists
Male
Motivation
Papio
Self Administration
Treatment Outcome
gamma-Aminobutyric Acid