Genetic Correlation Between Innate Alcohol Preference and Fear‐Potentiated Startle in Selected Mouse Lines

Abstract

There is a high rate of co-occurrence between anxiety and alcohol-use disorders in humans that may arise from the inheritance of common genes that increase the risk for both psychiatric disorders. The purpose of this study was to investigate whether a genetic relationship exists between innate alcohol preference and propensity to develop learned fear, using the fear-potentiated startle (FPS) paradigm, in 2 mouse lines selectively bred for high or low alcohol preference. Alcohol-naïve, male, and female mice from replicate pairs of lines selectively bred for high alcohol preference and low alcohol preference were randomly assigned to a fear-conditioned or control group. Mice in the fear-conditioned group received 20 pairings of a light stimulus and footshock; the control group received the same number of exposures to light and footshock, except that these stimuli were explicitly unpaired. During testing for FPS, acoustic stimuli were presented both in the presence and in the absence of the light stimulus. In both replicate pairs of lines, mice selectively bred for high alcohol preference showed greater FPS than mice selectively bred for low alcohol preference. No sex differences in FPS were found in any line. Control groups did not show FPS. These findings suggest that common genes mediate both innate alcohol preference and propensity to develop learned fear in these selected mouse lines.