Differential effects of quinine adulteration of alcohol on seeking and drinking.

Alcohol dependence is characterized by compulsive alcohol use. Alcohol-paired stimuli can drive compulsive alcohol use, induce craving, and lead to relapse. Alcohol dependence is highly heritable, and individuals with a family history are at elevated risk to develop an alcohol use disorder. Understanding the association between genetic vulnerability to alcohol dependence and neural alterations that promote an addiction phenotype are critical to the prevention and treatment of alcohol dependence. Here we use selectively bred alcohol-preferring P rats and their progenitor strain, Wistar rats, to investigate the relationship between genetic liability and alcohol-seeking and drinking behaviors in a discriminative stimuli paradigm. To further investigate strain differences in motivated responding, alcohol was adulterated with quinine, and intake and responding were assessed. While both strains learned to discriminate between stimuli that predicted alcohol availability, P rats learned faster and consumed more alcohol. Quinine adulteration reduced ethanol intake in both strains with no effect on ethanol-seeking measures. These data suggest genetic vulnerability to alcohol dependence is associated with increased motivated behaviors and highlight the utility of P rats in teasing apart the neural mechanisms associated with this phenotype. Additionally, these data suggest a dissociation between the neural systems that engage ethanol drinking versus compulsive ethanol seeking.