Combining non-linear and spectral cardiac variability metrics differentiates rat alcohol drinking with and without challenge

Alcohol Use Disorder (AUD) remains a substantial global challenge, with notable individual and sex differences. Heart rate variability (HRV) offers a potential link into the autonomic system underlying alcohol drinking. While simpler, time-domain HRV metrics have been explored, non-linear indicators could provide unique insights into more complex states like compulsive drinking, intake that persists despite negative consequences. We examined heart rate traces from male and female rats during intake of alcohol-only and alcohol+10mg/L quinine, a putative compulsive drinking model. In particular, we re-analyzed previously published findings, but newly focused on several non-linear HRV metrics: the Poincare ratio (possibly reflecting sympathovagal balance) and MultiScale entropy (MSE, perhaps reflecting unpredictability in broader and narrower time windows), along with the previously unexamined spectral HRV metrics (the parasympathetic indictor high-frequency HRV, HF-HRV%). HRV was assessed for the first ~1100 heart beats (~2.5 minutes), to assess HRV correlates of greater alcohol front-loading while having approximately similar amount of data per session. Lower Poincare ratio and higher HF-HRV% were overall related to higher alcohol consumption. In contrast, compulsive drinking, but not alcohol-only, was associated with lower broader-window HRV entropy, which was more pronounced in males. Drinking- and sex-related patterns were further identified using Principle Component Analysis, Ordinary Least Squares, and Linear Mixed Models. Limitations included perhaps being underpowered to detect significant relationships, especially in females. Thus, our preliminary findings suggest that combining HRV metrics could represent useful biomarkers for consumption levels during front-loading, which distinguished general intake from compulsion.