Genetic Correlation between Alcohol Preference and Motor Impulsivity with Genetically Selected High-Alcohol and Low-Alcohol Preferring Lines of Mice

Abstract

Alcohol related problems and abuse continue to be serious problems in the U.S. today affecting nearly 17.6 million Americans. Understanding of the specific genes and related behaviors associated with alcohol use may provide substantial preventative measures for those who are at an increased risk. Genetically selected lines such as the high-alcohol preferring (HAP) and low-alcohol preferring (LAP) mice have been created to examine which endophenotypes co-segregate with alcohol preference. One behavioral trait that has been commonly associated with alcohol related problems is impulsivity. Impulsivity is the inability to withhold a response (motor impulsivity) or to act without forethought (cognitive impulsivity). The latter comprises much of the research and literature today using delay discounting models to tease out differences in subject’s wiliness to discount larger reinforcers for smaller immediate reinforcers. This study utilized relatively two newer paradigms associated with motor impulsivity in attempt to test differences in response disinhibition between two independent replicate HAP and LAP lines. It is hypothesized that the genes responsible for alcohol preference would be genetically correlated with motor impulsivity as HAP mice would display a greater degree of response disinhibition. Two independent replicates consisting of 48 mice (24 HAP II and 24 LAP II, representing the 37th generation; 24 HAP III and 24 LAP III, representing the 13th generation) were tested in two separate identical experiments. Each experiment was comprised of three phases. Phase I utilized a fixed interval (FI) 120s procedure for 30 days. After the 30 days of FI exposure mice were immediately moved to phase II for 10 days which implored a differential reinforcement of low rate procedure (DRL) at a time interval of 20s. Phase III used the same procedures as Phase II except the DRL was increased to 32s. As hypothesized, there was a moderate genetic correlation between alcohol preference and impulsivity as the HAP II mice displayed greater response disinhibition throughout all three phases compared to the LAP II mice. No differences were observed amongst the replicate III mice in any of the three phases. The findings from this study provide additional support that a genetic correlation between alcohol preference and impulsivity exists as seen in the delay discounting literature. Though this was observed in only one of the two replicates, interpretations must be taken at caution as the replicate III mice are still in the early stages of selection. It is possible at this stage in the selection process that increases in alcohol over successive generations are associated with selecting for taste until a threshold is met where selection shifts to pharmacologic drinking relevance. Until later generations of replicate III mice are studied where pharmacologic drinking occurs, conclusions from this study provide a moderate genetic correlation between alcohol preference and impulsivity.