ABSTRACT
A defining characteristic of individuals diagnosed with alcohol use disorder (AUD) is that negative outcomes related to drinking do not lead them to reduce their alcohol use. In rodent models of AUD, this characteristic has been studied by adding the bitter tastant quinine to an ethanol solution. In this study, we extended this approach to a nonhuman primate model in which the ability of quinine to decrease the choice of a 4% ethanol solution vs. water was measured. Five adult female rhesus monkeys with 7.3 years of experience drinking ethanol were given access to a 4% ethanol solution and water for 3 h per day. When ethanol choice was stable, a single quinine concentration (0.03-5.6 g /L) was added to the ethanol solution for 1 day until a quinine concentration-effect curve was generated. After determining the quinine concentration that reduced ethanol choice by half (the quinine EC 50 ), the relative reinforcing strength of ethanol was manipulated by adding quinine or sucrose to the water alternative depending on the monkey's baseline choice. Adding quinine to ethanol produced a concentration-dependent decrease in ethanol choice and intake. Importantly, water intake increased, indicating an effect on response allocation rather than simply a decrease in fluid consumption. Consistent with this conclusion, the addition of quinine or sucrose to the water alternative resulted in predictable increases and decreases, respectively, in ethanol choice. These studies establish a model of punishment of ethanol choice in nonhuman primates that can be used to understand the contextual, biologic and pharmacologic factors that influence sensitivity to the punishment of alcohol drinking.
