Effects of the benzodiazepine GABAA α1-preferring ligand, 3-propoxy-β-carboline hydrochloride (3-PBC), on alcohol seeking and self-administration in baboons

Abstract

Rationale: The various α subtypes of GABAA receptors have been strongly implicated in alcohol reinforcement and consumption.

Objectives: 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).

Methods: 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.

Results: 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).

Conclusions: The results support the involvement of the GABAA α1 subtype receptor in alcohol reinforcement and consumption.

Fig. 1

Experiment 2: The effects of repeated (5 day) administration of 3-PBC on self-administration in C3 of the CSR in (a) the Alcohol Group and (b) the Control Group. Data shown are the group means (± SEM) of right (self-administration) responses (left panels) and for the alcohol group, change in g/kg of alcohol consumed (right panel). * indicates p<0.05 for pairwise comparison for each dose vs. baseline

Fig. 2

Experiment 2: The effects of repeated (5 day) administration of 3-PBC on the pattern and number of drinks per 20-min interval of the 120-min self-administration period (C3) in the (a) Alcohol Group and (b) the Control Group. Data shown are group mean drinks (+ SEM) for each successive time bin of availability of alcohol or the non-alcoholic beverage, and * indicates p<0.05 for pairwise comparison for each 3-PBC dose vs. vehicle within each time bin