Effects of the benzodiazepine GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons
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- Kaminski, B.J., Van Linn, M.L., Cook, J.M. et al. Psychopharmacology (2013) 227: 127. doi:10.1007/s00213-012-2946-z
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The various α subtypes of GABAA receptors have been strongly implicated in alcohol reinforcement and consumption.
The effects of the GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on seeking and self-administration responses were evaluated in two groups of baboons trained under a 3-component chained schedule of reinforcement (CSR).
Alcohol (4 % w/v; n = 5; alcohol group) or a preferred nonalcoholic beverage (n = 4; control group) was available for self-administration only in component 3 of the CSR. Responses in component 2 provided indices of motivation to drink (seeking). 3-PBC (1.0–30.0 mg/kg) and saline were administered before drinking sessions under both acute and 5-day dosing conditions.
Repeated, and not acute, doses of 3-PBC significantly decreased total self-administration responses (p < 0.05), volume consumed (p < 0.05), and gram per kilogram of alcohol (p < 0.05) in the alcohol group. In the control group, 5-day administration of 3-PBC significantly decreased total self-administration responses (p < 0.05) but produced nonsignificant decreases in volume consumed. Within-session pattern of drinking was characterized by a high level of drinking in the first 20 min of the session for both groups, which was significantly (p < 0.05) decreased by all doses of 3-PBC (1.0–18.0 mg/kg) only in the alcohol group. In contrast, the first drinking bout in the control group was only reduced at the highest doses of 3-PBC (10.0 and 18.0 mg/kg).
The results support the involvement of the GABAA α1 subtype receptor in alcohol reinforcement and consumption.