Follow Your Heart: Heart Rate Variability Reveals Sex Differences in Autonomic Regulation During Anxiety-Like Behavior and During Alcohol Drinking in Rats

Abstract

Mental health conditions remain a substantial and costly challenge to society. Of note, women have a higher prevalence of anxiety disorders than men, and alcohol misuse in women has risen sharply in recent years. However, critical mechanisms underlying these observed sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect dynamic balance between the two opposing branches of the autonomic nervous system: sympathetic (SNS, “fight or flight”) and parasympathetic (PNS, “rest and digest”). Furthermore, recent evidence strongly suggests these measures are potential biomarkers for pathological states, including mental health conditions. To better understand sex differences in autonomic mechanisms related to pathological anxiety and alcohol misuse, we utilized cardiac telemetry to measure HR and HRV. This allowed observation of real-time autonomic tone in awake, freely behaving Wistar rats of both sexes. At baseline, female rats had greater HR and lower SNS influence than males, which concords with human studies. In both anxiety-like behavior and alcohol drinking studies, we observed that females tend to utilize a higher PNS influence to overcome challenge, whereas males tend to utilize higher SNS. Furthermore, female (but not male) baseline HR and HRV are related to within-task behavior, suggesting that baseline state impacts drinking and anxiety-like behavior in a sex-specific way. Again, these data concord with human research suggesting a similar PNS bias in women and SNS bias in men when responding, especially under challenge. Taken together, these data have contributed new knowledge to sex differences in autonomic engagement, especially for anxiety states and alcohol drinking. Importantly, these findings are likely translationally relevant for the development of novel, and more personalized, therapies.