Modeling ultrasonic vocalization profiles as predictive biomarkers for alcohol consumption susceptibility

The overarching goal of this dissertation project is to characterize the ultrasonic vocalization profiles associated with sex differences and predisposition for alcohol consumption in rodents. In order to accomplish this goal we pursued the following specific aims: 1) to investigate potential sex differences in the USV profiles of 50 – 55 kHz frequency modulated (FM) and 22 – 28 kHz calls in male and female high-alcohol-drinking (HAD-1) rats, 2) to investigate potential differences in the counts and acoustic characteristics of 50 – 55 kHz FM and 22 – 28 kHz USVs between HAD-1 and low-alcohol-drinking (LAD-1) rats, and 3) to determine whether USV profiles can serve as biomarkers for the predisposition to consume high levels of alcohol in Long-Evans rats. The results from the studies assessing the first aim are described in chapters 2 and 3. We found that male and female HAD-1 rats spontaneously emit large amounts of unprovoked 50 – 55 kHz FM and 22 – 28 kHz USVs with distinct acoustic properties, which are further susceptible to modulation by ethanol. We also found that female HAD-1 rats show enhanced exploratory activity in an object recognition task, and that these exploratory behaviors predict future alcohol consumption levels in male and female HAD-1 rats. The results for the second aim are described in chapter 4, where we show that USV acoustic profiles can be used to generate machine learning classification models, which can discriminate between HAD-1 and LAD-1 rats with very high accuracy. The results for the third aim are described in chapter 5, where we show that USV data from alcohol-naïve rats across five different rat lines is significantly correlated with predisposition alcohol consumption. Here we provide direct evidence that USV data collected from alcohol-naïve, adult, male Long-Evans rats can be used to predict future alcohol consumption in these rats. In chapter 6, we further characterize changes in the total counts and acoustic characteristics of spontaneously emitted USVs due to age and ethanol exposure in adult, male Long-Evans rats. We finish in chapter 7 by summarizing the results and discussing the implications, as well as, potential future directions of this work.