Several of the diagnostic criteria for alcohol use disorder (AUD) reflect the fact that some people continue to drink despite negative consequences. That is, vulnerable individuals are resistant to punishment. A better understanding of the behavioral and neurobiological factors that underlie this characteristic will lead to better preventive and treatment approaches to AUD. The objective of this study was to extend rodent studies by developing and validating a model of resistance to punishment of alcohol drinking in nonhuman primates. To increase translational relevance, the study was conducted in the context of an ethanol-water choice procedure. Each day two 800-ml bottles were hung on the monkey’s home cage for three hours, one containing a 4% ethanol solution and the other containing water. The primary dependent variable was ethanol choice (ml of ethanol consumed divided by total ml consumed x 100). When choice was stable (±10% of the 3-day mean with no upward or downward trend), several manipulations were made. Experiment 1 characterized choice of several concentrations of ethanol (0%-8%) versus water by substituting other ethanol concentrations for the 4% solution until choice again stabilized. The relationship between the available ethanol concentration and ethanol choice was characterized by an inverted U-shaped function. In Experiment 2, the alternative (water) was manipulated to further validate the procedure as a model of choice. For monkeys in whom choice of the 4% ethanol solution was relatively low (lt;30%), the bitter tastant quinine (0.01-1.0 g/L) was added to the water solution. For monkeys with higher choice of 4% ethanol (gt;70%), sucrose (1.0-5.0%) was added to the water solution. These manipulations predictably increased and decreased, respectively, choice of the 4% ethanol solution. Finally, in Experiment 3, consumption of the 4% ethanol solution was punished by adding quinine (0.01-5.6 g/L) to the ethanol solution. Increasing quinine concentrations decreased ethanol choice and ethanol intake in all monkeys without decreasing the total volume of fluid consumed. Individual differences were observed in the potency of quinine which can be interpreted as individual differences in sensitivity to punishment. These studies established and validated a novel nonhuman primate model of punishment of ethanol choice which can be used to characterize factors that underlie susceptibility versus resistance to punishing effects of adverse consequences of alcohol drinking.
