Dominiquini-Moraes Beatriz, Bernardes-Ribeiro Mariana, Patrone Luis Gustavo A, Fonseca Elisa M, Frias Alana T, Silva Kaoma S Costa, Araujo-Lopes Roberta, Szawka Raphael E, Bícego Kênia C, Zangrossi Hélio, Gargaglioni Luciane H
Department of Animal Morphology and Physiology, College of Agricultural and Veterinarian Sciences, São Paulo State University, Rod. Prof. Paulo Donato Castellane S/N, Jaboticabal, SP, 14884-900, Brazil.
Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Pflugers Arch. 2025 Mar;477(3):349-369. doi: 10.1007/s00424-024-03040-w. Epub 2024 Nov 27.
The prevalence of panic disorder is two to four times higher in women compared to that in men, and hormonal changes during the menstrual cycle play a role in the occurrence of panic attacks. Here, we investigated the effect of the estrous cycle on the ventilatory and behavioral responses to CO in mice. Female mice in proestrus, estrus, metestrus, or diestrus were exposed to 20% CO, and their escape behaviors, brain monoamines, and plasma levels of 17β-estradiol (E) and progesterone (P) were measured. Pulmonary ventilation (V̇), oxygen consumption (V̇O), and body core temperature (T) were also measured during normocapnia followed by CO. Females exposed to 20% CO exhibited an escape behavior, but the estrous cycle did not affect this response. Females in all phases of the estrous cycle showed higher V̇ and lower T during hypercapnia. In diestrus, there was an attenuation of CO-induced hyperventilation with no change in V̇O, whereas in estrus, this response was accompanied by a reduction in V̇O. Hypercapnia also increased the concentration of plasma P and central DOPAC, the main dopamine metabolite, in all females. There was an estrous cycle effect on brainstem serotonin, with females in estrus showing a higher concentration than females in the metestrus and diestrus phases. Therefore, our data suggest that hypercapnia induces panic-related behaviors and ventilatory changes that lead to an increase in P secretion in female mice, likely originating from the adrenals. The estrous cycle does not affect the behavioral response but interferes in the ventilatory and metabolic responses to CO in mice.
惊恐障碍的患病率女性比男性高两到四倍，月经周期中的激素变化在惊恐发作的发生中起作用。在此，我们研究了发情周期对小鼠对一氧化碳的通气和行为反应的影响。将处于动情前期、发情期、动情后期或动情间期的雌性小鼠暴露于20%的一氧化碳中，并测量它们的逃避行为、脑单胺以及血浆中17β-雌二醇（E）和孕酮（P）的水平。在正常碳酸血症后再给予一氧化碳期间，还测量了肺通气量（V̇）、耗氧量（V̇O）和体核温度（T）。暴露于20%一氧化碳的雌性小鼠表现出逃避行为，但发情周期并未影响这种反应。发情周期各阶段的雌性小鼠在高碳酸血症期间均表现出较高的V̇和较低的T。在动情间期，一氧化碳诱导的过度通气减弱，V̇O无变化，而在发情期，这种反应伴随着V̇O的降低。高碳酸血症还使所有雌性小鼠血浆P和主要多巴胺代谢产物中枢3,4-二羟基苯乙酸（DOPAC）的浓度升高。发情周期对脑干5-羟色胺有影响，发情期的雌性小鼠其浓度高于动情后期和动情间期的雌性小鼠。因此，我们的数据表明，高碳酸血症诱导了与惊恐相关的行为和通气变化，导致雌性小鼠P分泌增加，可能源自肾上腺。发情周期不影响行为反应，但会干扰小鼠对一氧化碳的通气和代谢反应。
