Zakiniaeiz Yasmin, Gueorguieva Ralitza, Peltier MacKenzie R, Verplaetse Terril L, Roberts Walter, McKee Sherry A, Cosgrove Kelly P
Department of Psychiatry, School of Medicine, Yale University, New Haven, CT, United States.
Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, United States.
Front Behav Neurosci. 2023 Jun 9;17:1192740. doi: 10.3389/fnbeh.2023.1192740. eCollection 2023.
Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls.
Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. DR availability () at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone.
Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC .
DISCUSSION/CONCLUSION: This study demonstrated that lower estradiol levels are associated with lower dlPFC DR availability in women which may underlie difficulty resisting smoking.
吸烟存在性别差异。女性戒烟比男性更困难。吸烟是由尼古丁的强化作用驱动的，尼古丁是香烟中的主要成瘾成分。尼古丁与烟碱型乙酰胆碱受体结合，促进纹状体和皮质脑区的多巴胺释放。背外侧前额叶皮层（dlPFC）中多巴胺D受体信号失调与认知缺陷有关，如注意力、学习和抑制控制方面的障碍，这些障碍会阻碍戒烟尝试。雌激素和孕酮等性类固醇激素通过多巴胺能作用影响药物使用行为，表明它们的影响可能解释吸烟中的性别差异。本研究的目的是将吸烟人群和健康对照者的dlPFC多巴胺指标与性类固醇激素水平联系起来。
24名（12名女性）吸烟者和25名性别和年龄匹配的对照者参加了两次同日的[C]FLB457正电子发射断层扫描，一次在服用苯丙胺之前，一次在服用苯丙胺之后。计算基线和服用苯丙胺后的DR可用性（）。在同一天，采集血浆样本分析性类固醇激素水平：雌二醇、孕酮和游离睾酮。
吸烟女性的雌二醇水平比与其性别匹配的对照者略低。吸烟男性的雌二醇水平较高，游离睾酮水平比与其性别匹配的对照者略高。仅在女性中，较低的雌二醇水平与服用苯丙胺前较低的dlPFC显著相关。
讨论/结论：本研究表明，较低的雌二醇水平与女性较低的dlPFC DR可用性相关，这可能是女性难以抵抗吸烟的原因。
