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Prenatal nicotine sex-dependently alters adolescent dopamine system development.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41398-019-0640-1 Jennifer B Dwyer 1 , Anjelica Cardenas 1 , Ryan M Franke 1 , YiLing Chen 1 , Yu Bai 2 , James D Belluzzi 1 , Shahrdad Lotfipour 1, 2 , Frances M Leslie 1, 3
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41398-019-0640-1 Jennifer B Dwyer 1 , Anjelica Cardenas 1 , Ryan M Franke 1 , YiLing Chen 1 , Yu Bai 2 , James D Belluzzi 1 , Shahrdad Lotfipour 1, 2 , Frances M Leslie 1, 3
Affiliation
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Despite persistent public health initiatives, many women continue to smoke during pregnancy. Since maternal smoking has been linked to persisting sex-dependent neurobehavioral deficits in offspring, some consider nicotine to be a safer alternative to tobacco during pregnancy, and the use of electronic nicotine delivery systems is on the rise. We presently show, however, that sustained exposure to low doses of nicotine during fetal development, approximating plasma levels seen clinically with the nicotine patch, produces substantial changes in developing corticostriatal dopamine systems in adolescence. Briefly, pregnant dams were implanted on gestational day 4 with an osmotic minipump that delivered either saline (GS) or nicotine (3 mg/kg/day) (GN) for two weeks. At birth, pups were cross-fostered with treatment naïve dams and were handled daily. Biochemical analyses, signaling assays, and behavioral responses to cocaine were assessed on postnatal day 32, representative of adolescence in the rodent. GN treatment had both sex-dependent and sex-independent effects on prefrontal dopamine systems, altering Catechol-O-methyl transferase (COMT)-dependent dopamine turnover in males and norepinephrine transporter (NET) binding expression in both sexes. GN enhanced cocaine-induced locomotor activity in females, concomitant with GN-induced reductions in striatal dopamine transporter (DAT) binding. GN enhanced ventral striatal D2-like receptor expression and G-protein coupling, while altering the roles of D2 and D3 receptors in cocaine-induced behaviors. These data show that low-dose prenatal nicotine treatment sex-dependently alters corticostriatal dopamine system development, which may underlie clinical deficits seen in adolescents exposed to tobacco or nicotine in utero.
中文翻译：
产前尼古丁的性别依赖性改变了青少年多巴胺系统的发育。
尽管采取了持续的公共卫生措施，但许多妇女在怀孕期间仍在吸烟。由于母亲吸烟与后代持续存在的性别依赖性神经行为缺陷有关，因此有人认为尼古丁在怀孕期间是替代烟草的更安全替代方法，并且电子尼古丁传送系统的使用正在增加。然而，我们目前显示，在胎儿发育过程中持续暴露于低剂量的尼古丁，接近临床上用尼古丁贴片所见的血浆水平，在青春期发育中的皮质口多巴胺系统中产生了实质性变化。简而言之，在妊娠第4天，用渗透性微型泵植入怀孕的水坝，该微型泵输送生理盐水（GS）或尼古丁（3 mg / kg / day）（GN），持续两周。幼崽在出生时就与幼稚的水坝进行了交叉养育，并每天进行处理。在出生后第32天评估了可卡因的生化分析，信号传导测定和行为反应，代表了啮齿动物的青春期。GN治疗对前额叶多巴胺系统既有性别依赖性又有性别依赖性，改变了男性邻苯二酚-O-甲基转移酶（COMT）依赖性多巴胺周转率和男女的去甲肾上腺素转运蛋白（NET）结合表达。GN增强了可卡因诱导的女性自发运动，并伴有GN诱导的纹状体多巴胺转运蛋白（DAT）结合减少。GN增强了腹侧纹状体D2样受体表达和G蛋白偶联，同时改变了D2和D3受体在可卡因诱导的行为中的作用。这些数据表明，低剂量的产前尼古丁治疗会性别依赖性地改变皮质上皮多巴胺系统的发育，
更新日期：2019-11-18
中文翻译：
产前尼古丁的性别依赖性改变了青少年多巴胺系统的发育。
尽管采取了持续的公共卫生措施，但许多妇女在怀孕期间仍在吸烟。由于母亲吸烟与后代持续存在的性别依赖性神经行为缺陷有关，因此有人认为尼古丁在怀孕期间是替代烟草的更安全替代方法，并且电子尼古丁传送系统的使用正在增加。然而，我们目前显示，在胎儿发育过程中持续暴露于低剂量的尼古丁，接近临床上用尼古丁贴片所见的血浆水平，在青春期发育中的皮质口多巴胺系统中产生了实质性变化。简而言之，在妊娠第4天，用渗透性微型泵植入怀孕的水坝，该微型泵输送生理盐水（GS）或尼古丁（3 mg / kg / day）（GN），持续两周。幼崽在出生时就与幼稚的水坝进行了交叉养育，并每天进行处理。在出生后第32天评估了可卡因的生化分析，信号传导测定和行为反应，代表了啮齿动物的青春期。GN治疗对前额叶多巴胺系统既有性别依赖性又有性别依赖性，改变了男性邻苯二酚-O-甲基转移酶（COMT）依赖性多巴胺周转率和男女的去甲肾上腺素转运蛋白（NET）结合表达。GN增强了可卡因诱导的女性自发运动，并伴有GN诱导的纹状体多巴胺转运蛋白（DAT）结合减少。GN增强了腹侧纹状体D2样受体表达和G蛋白偶联，同时改变了D2和D3受体在可卡因诱导的行为中的作用。这些数据表明，低剂量的产前尼古丁治疗会性别依赖性地改变皮质上皮多巴胺系统的发育，
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