Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
Compr Psychiatry. 2023 May;123:152381. doi: 10.1016/j.comppsych.2023.152381. Epub 2023 Mar 5.
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.
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 [C]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 [C]cetrozole non-displaceable binding potential.
The highest availability of aromatase was found in the right and left thalamus. Upon nicotine exposure, [C]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.
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.
女性心理健康领域的研究表明，大量研究表明尼古丁成瘾和治疗反应存在性别差异，但这些差异的神经内分泌基础在很大程度上仍不清楚。涉及性激素的途径可能确实参与了尼古丁的行为效应，因为已经发现它分别在体外和体内的啮齿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，在边缘大脑中高度表达。
本研究旨在调查健康女性暴露于尼古丁时体内芳香酶的可用性。进行结构磁共振成像和两次 [C] 他唑来膦酸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。测量了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 的方法评估 [C] 他唑来膦酸不可置换结合潜能的变化。
芳香酶的最高可用性在右和左丘脑。在暴露于尼古丁后，丘脑双侧的 [C] 他唑来膦酸结合被急性减少（Cohen's d = -0.99）。与此一致，可替宁水平与丘脑芳香酶的可用性呈负相关，尽管呈非显著趋势。
这些发现表明尼古丁在丘脑区域急性阻断芳香酶的可用性。这表明了一种新的、可能的机制，介导了尼古丁对人类行为的影响，特别是与尼古丁成瘾中的性别差异有关。
