The central amygdala (CeA) plays a critical role in integrating emotional and autonomic responses, including sympathetic outflow. Ethanol influences activity of CeA and autonomic regulation, contributing to stress-induced alcohol drinking, yet the contribution of its metabolite acetate and potential sex differences in these central effects remain unclear. We hypothesized that ethanol microinjection into the CeA would increase splanchnic sympathetic nerve activity (SSNA) in a sex-dependent manner, with greater activation in females, and that acetate would produce similar effects if ethanol’s actions are mediated in part by its metabolite. This study examined the influence of ethanol and acetate microinjection into the CeA on SSNA in male and female rats. Adult male and female Sprague–Dawley rats were anesthetized with urethane and α-chloralose. A recording electrode was placed on the splanchnic sympathetic nerve for continuous splanchnic sympathetic nerve activity (SSNA) measurement. Following baseline recording, either ethanol (1.7 µmol/100nL/side) or sodium acetate (0.2 µmol/100nL/side) was bilaterally microinjected into the CeA. Nerve activity was monitored for approximately 2 hours post-injection, and responses were quantified as percent change from baseline. Ethanol microinjection into the CeA produced an excitatory effect on SSNA in both sexes, with a greater response in females (n = 5, 133.6 ± 30.24%, ) compared to males (n = 8, 74.96 ± 11.63%, P < 0.05). Acetate microinjection also increased SSNA and demonstrated a pronounced sex difference, with females exhibiting a significantly greater response (n = 5, 147.3 ± 6.0%) than males (n = 9, 84.34 ± 14.7%, p < 0.05). These findings indicate that both ethanol and acetate within the CeA elevate sympathetic drive, demonstrating the CeA’s pivotal role in central autonomic regulation. The similar female-biased enhancement observed with acetate suggests that ethanol-induced sympathetic activation in the CeA may be mediated, at least in part, through its metabolism to acetate, and that sex-dependent differences in this pathway contribute to exaggerated sympathetic responses in females. Together, these results provide new insight into the neural mechanisms by which ethanol and its metabolites modulate autonomic activity and highlight the importance of considering sex as a biological variable in studies of central ethanol effects. Funding: NIHR15HL122952 and NIHR01HL163159. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Heaman et al. (Fri,) studied this question.