TY - JOUR
T1 - Effects of the benzodiazepine GABAA α1-preferring antagonist 3-isopropoxy-β-carboline hydrochloride (3-ISOPBC) on alcohol seeking and self-administration in baboons
AU - Holtyn, August F.
AU - Tiruveedhula, V. V.N.Phani Babu
AU - Stephen, Michael Rajesh
AU - Cook, James M.
AU - Weerts, Elise M.
N1 - Funding Information:
The authors thank Margot Ernst, Petra Scholze, and Xenia Simeone for providing data on the binding affinity of 3-ISOPBC. Psychoactive drug screening program data were generously provided by the National Institute of Mental Health's Psychoactive Drug Screening Program, Contract # HHSN-271-2013-00017-C (NIMH PDSP). The NIMH PDSP is Directed by Bryan L. Roth, MD, PhD at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscoll at NIMH, Bethesda, MD.
Funding Information:
This work was supported by the National Institutes of Health under grant numbers R01AA15971 (Weerts), R01MH096463 (Cook), and R01NS076517 (Cook). The grants provided financial support for the conduct of the research and the preparation of the article. The funding sponsors were not involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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 (5.0–30.0 mg/kg) and vehicle were administered before drinking sessions under both acute and chronic (5 day) 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.
AB - 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 (5.0–30.0 mg/kg) and vehicle were administered before drinking sessions under both acute and chronic (5 day) 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.
KW - 3-ISOPBC
KW - 3-Isopropoxy-β-carboline hydrochloride
KW - Alcohol
KW - Baboon
KW - Self-administration
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U2 - 10.1016/j.drugalcdep.2016.10.036
DO - 10.1016/j.drugalcdep.2016.10.036
M3 - Article
C2 - 27865151
AN - SCOPUS:84995700083
SN - 0376-8716
VL - 170
SP - 25
EP - 31
JO - Drug and alcohol dependence
JF - Drug and alcohol dependence
ER -