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

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.