Oral self-administration of ethanol, phencyclidine, methadone, pentobarbital and quinine in rhesus monkeys

Abstract 

Rationale: Simultaneous and sequential drug use among clinical populations is the norm, whereas the pattern of self-administration of multiple drugs among non-human primate populations has not been thoroughly explored. Objectives: To determine the relationship between the preferences and intakes of a large group of rhesus monkeys exposed to various orally available solutions. Methods: Thirteen male and eleven female young adult rhesus monkeys (Macaca mulatta) were exposed to orally available drug solutions using a concurrent choice (drug and water) procedure, where fluid delivery was made contingent upon single spout contacts (fixed ratio one). Results: Ethanol (0.25–16% w:v) produced biphasic effects on the number of fluid deliveries obtained, with peak ethanol preferences over water demonstrated at the 1–2% w:v concentrations. No preferences for the N-methyl-d-aspartate receptor antagonist phencyclidine or water were demonstrated at lower concentrations (0.0078125–0.125 mg/ml) and, at higher concentrations (0.25, 0.5 mg/ml), a preference for water was demonstrated. The µ opioid receptor agonist methadone (0.001–0.3 mg/ml) and the prototypic bitter substance quinine (0.001–0.3 mg/ml) failed to produce preferences for drug or water. A large preference for water over the barbiturate pentobarbital (0.01–3 mg/ml) was also demonstrated. After rank-ordering the subjects based on their drug preferences or intakes, modest to no correlations across drugs were demonstrated. Conclusions: These results reveal that a robust ethanol preference is not predictive of a preference for drugs of abuse from other classes and suggests that fluid intakes were correlated, irrespective of the presence or absence of drug in the solution.