The long-term objective of this proposal is to identify new biological markers that identify individuals at high risk of abusing alcohol. Abuse of alcohol is detrimental to society in numerous ways including lost productivity, increased medical costs, and loss of human life due to the direct or indirect actions of alcohol. Identifying traits or characteristics that predispose an individual to alcohol abuse may lead to novel targets for the treatment of alcohol abuse, and enhanced prevention. Individuals that abuse alcohol and other drugs commonly exhibit heightened impulsivity. Impulsivity may precipitate initial use of alcohol, may facilitate dependence and/or may be affected by alcohol itself. The proposed project will explore the relationship between impulsivity, and the genes associated with alcohol consumption. This project will use rats selectively bred to drink high (HAD) or low (LAD) amounts of alcohol. The first component of the project is to assess baseline levels of impulsivity in these rat lines. Two measures of impulsivity will be taken, one that measures impulsive choice (delay discounting), and one that measures impulsive action (Go/No-go task). Delay discounting determines the decreased value placed on rewards that are given after a delay. Increased impulsivity in this task is demonstrated by a stronger preference for smaller immediate rewards over larger delayed rewards. The Go/No-go task measures the ability of the subject to withhold a response in the presence of specific cues. This procedure provides a number of measures of impulsivity including: false-alarms (incorrect responses during No-go trials), efficiency (total number of rewards earned/total number of lever presses), and responses during the pre-cue period (responses during the period immediately preceding the beginning of a new trial). We propose that HAD rats will respond more impulsively than LAD rats in both delay discounting and go/no-go tasks. After baseline levels of responding on these tasks are established, animals will be injected with alcohol to determine if alcohol affects responding, or differentially affects responding on impulsivity and risk-taking tasks by HAD or LAD rats. We hypothesize that alcohol treatment will increase impulsive responding on both delay discounting and Go/No- go tasks. We further hypothesize that the magnitude of the alcohol effect will be larger in HAD, than LAD rats, suggesting that HAD rats are more sensitive to alcohol treatment than LAD rats. The results of this study will provide new insight into the genetic connection between alcohol drinking and impulsivity may identify characteristics that promote addiction.
| Wilhelm, Clare J; Mitchell, Suzanne H (2010) Response bias is unaffected by delay length in a delay discounting paradigm. Behav Processes 84:445-9 |
| Wilhelm, C J; Mitchell, S H (2009) Strain differences in delay discounting using inbred rats. Genes Brain Behav 8:426-34 |
