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Item Follow Your Heart: Heart Rate Variability Reveals Sex Differences in Autonomic Regulation During Anxiety-Like Behavior and During Alcohol Drinking in Rats(2024-02) Frasier, Raizel Michele; Yoder, Karmen; Hopf, Woody; McKinzie, David; Lukkes, Jodi; Conroy, SusanMental 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.Item Heart rate variability measures indicating sex differences in autonomic regulation during anxiety-like behavior in rats(Frontiers Media, 2023-10-31) Frasier, Raizel M.; De Oliveira Sergio, Thatiane; Starski, Phillip A.; Grippo, Angela J.; Hopf, F. Woodward; Psychiatry, School of MedicineIntroduction: Mental health conditions remain a substantial and costly challenge to society, especially in women since they have nearly twice the prevalence of anxiety disorders. However, critical mechanisms underlying sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect balance between sympathetic (SNS) and parasympathetic (PNS) systems and are potential biomarkers for pathological states. Methods: To better understand sex differences in anxiety-related autonomic mechanisms, we examined HR/HRV telemetry in food-restricted adult rats during novelty suppression of feeding (NSF), with conflict between food under bright light in the arena center. To assess HRV, we calculated the SDNN (reflective of both SNS and PNS contribution) and rMSSD (reflective of PNS contribution) and compared these metrics to behaviors within the anxiety task. Results: Females had greater HR and lower SNS indicators at baseline, as in humans. Further, females (but not males) with higher basal HR carried this state into NSF, delaying first approach to center. In contrast, males with lower SNS measures approached and spent more time in the brightly-lit center. Further, females with lower SNS indicators consumed significantly more food. In males, a high-SNS subpopulation consumed no food. Among consumers, males with greater SNS ate more food. Discussion: Together, these are congruent with human findings suggesting women engage PNS more, and men SNS more. Our previous behavior-only work also observed female differences from males during initial movement and food intake. Thus, high basal SNS in females reduced behavior early in NSF, while subsequent reduced SNS allowed greater food intake. In males, lower SNS increased engagement with arena center, but greater SNS predicted higher consumption. Our findings show novel and likely clinically relevant sex differences in HRV-behavior relationships.