Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study
Acute nicotine exposure blocks aromatase in the limbic brain of healthy women: A [11C]cetrozole PET study
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DOI：
10.1016/j.comppsych.2023.152381
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发表时间：
2023-03-10
影响因子：
7.3
通讯作者：
Comasco, Erika
中科院分区：
文献类型：
--
作者：
Dubol, Manon;Immenschuh, Jana;Comasco, Erika
背景：出于对女性心理健康的关注，大量研究表明尼古丁成瘾和治疗反应存在性别差异，但其心理神经内分泌基础仍然很大程度上未知。涉及性类固醇的途径确实可能与尼古丁的行为效应有关，因为人们发现尼古丁分别在体外和体内的啮齿类动物和非人类灵长类动物中抑制芳香酶。芳香酶调节雌激素的合成，并且与成瘾相关，在边缘脑中高度表达。方法：本研究旨在调查健康女性体内芳香酶的可用性与尼古丁暴露的关系。进行结构磁共振成像和两次[11C]西曲唑正电子发射断层扫描（PET）扫描，以评估尼古丁给药前后芳香酶的可用性。测量性腺激素和可替宁水平。鉴于芳香酶的区域特异性表达，采用基于 ROI 的方法来评估 [11C]cetrozole 不可置换结合潜力的变化。结果：在左右丘脑中发现芳香酶的利用率最高。接触尼古丁后，丘脑中的[11C]cetrozole 结合在双侧急剧减少（Cohen's d =-0.99）。与此一致的是，可替宁水平与丘脑中芳香酶的可用性呈负相关，尽管趋势不显着。结论：这些发现表明尼古丁在丘脑区域急性阻断芳香酶的利用。这表明了一种新的假定机制介导尼古丁对人类行为的影响，特别是与尼古丁成瘾的性别差异相关。
Background: Of interest to women's mental health, a wealth of studies suggests sex differences in nicotine addiction and treatment response, but their psychoneuroendocrine underpinnings remain largely unknown. A pathway involving sex steroids could indeed be involved in the behavioural effects of nicotine, as it was found to inhibit aromatase in vitro and in vivo in rodents and non-human primates, respectively. Aromatase regulates the synthesis of oestrogens and, of relevance to addiction, is highly expressed in the limbic brain. Methods: The present study sought to investigate in vivo aromatase availability in relation to exposure to nicotine in healthy women. Structural magnetic resonance imaging and two [11C]cetrozole positron emission tomography (PET) scans were performed to assess the availability of aromatase before and after administration of nicotine. Gonadal hormones and cotinine levels were measured. Given the region-specific expression of aromatase, a ROI -based approach was employed to assess changes in [11C]cetrozole non-displaceable binding potential. Results: The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [11C]cetrozole binding in the thalamus was acutely decreased bilaterally (Cohen's d =-0.99). In line, cotinine levels were negatively associated with aromatase availability in the thalamus, although as non-significant trend. Conclusions: These findings indicate acute blocking of aromatase availability by nicotine in the thalamic area. This suggests a new putative mechanism mediating the effects of nicotine on human behaviour, particularly relevant to sex differences in nicotine addiction.