Effects of naltrexone on alcohol drinking patterns and extinction of alcohol seeking in baboons

Abstract

Rationale: Understanding naltrexone's effect on motivation to drink and pattern of drinking is important for better treatment outcomes and for comparison with novel medications.

Objectives: Naltrexone's effects on number and pattern of seeking, self-administration, and extinction responses were evaluated in two groups of baboons trained under a three-component chained schedule of reinforcement (CSR).

Methods: Alcohol (4 % w/v; n = 4; 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). Naltrexone (0.32-3.2 mg/kg) and saline were administered before drinking and component 2 extinction sessions.

Results: Acute doses of naltrexone significantly decreased total self-administration responses (p < 0.01), intake volume (p < 0.001), and grams per kilogram of alcohol (p < 0.01) in the alcohol group only. Pattern of drinking did not change, but the number of drinks during the initial drinking bout was decreased significantly by naltrexone for both groups (p < 0.05). During within-session extinction tests, acute naltrexone significantly decreased time to reach extinction (p < 0.01) and number of seeking responses (p < 0.05), particularly early in the extinction period in the alcohol group only. When administered chronically, naltrexone did not decrease progressive ratio breaking points to gain access to alcohol, but dose dependently reduced alcohol self-administration (p < 0.05) by decreasing the magnitude of the initial drinking bout.

Conclusions: The results support clinical observations that naltrexone may be most effective at reducing self-administration in the context of ongoing alcohol availability and may reduce motivation to drink in the presence of alcohol-related cues.

Fig. 1

Experiment 1: the effects of acute naltrexone 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 number of right lever (drink) responses (left panels), change in volume from baseline (middle panels) and for the alcohol group, change in g/kg of alcohol consumed (right panels). Baseline (BL) g/kg intake was the average of the three days of alcohol self-administration that preceded each naltrexone dose or vehicle (V) test session. * indicates p<0.05 for pairwise comparison for each dose vs. baseline

Fig. 2

Experiment 1: The effects of acute naltrexone 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 naltrexone dose vs. vehicle within each time bin

Fig 3

Experiment 3: The effects of chronic naltrexone on motivation to obtain and self-administer alcohol in the Alcohol Group. Data shown for a) are the mean (± SEM) breaking point for each chronically administered naltrexone dose and vehicle (V). Data shown for b) are the mean (± SEM) of the first 5 days of chronic naltrexone dosing on right lever (drink) responses and change in g/kg alcohol self-administered. Data shown for c) are the mean (± SEM) of the first 5 days of chronic naltrexone dosing on number of drinks per 20-min interval of the 120-min alcohol self-administration period (C3). Other details as in Fig. 1 and 2

Fig 4

Experiment 4: Effects of acute naltrexone on extinction of seeking in the within-session extinction tests in C2-Link 2 for the (a) Alcohol Group and (b) the Control Group. Data shown are group mean (+ SEM) number of left lever responses per 10 min interval for the first 60 min of the within-session extinction test session and * indicates p<0.05 for pairwise comparison for each dose vs. vehicle within each interval