Williams Sarah K, Cox Elizabeth T, McMurray Matthew S, Fay Emily E, Jarrett Thomas M, Walker Cheryl H, Overstreet David H, Johns Josephine M
Curriculum in Neurobiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Neurotoxicol Teratol. 2009 Sep-Oct;31(5):291-302. doi: 10.1016/j.ntt.2009.06.001. Epub 2009 Jun 17.
Ethanol consumption and smoking during pregnancy are common, despite the known adverse effects on the fetus. The teratogenicity of each drug independently is well established; however, the effects of concurrent exposure to ethanol and nicotine in preclinical models remain unclear. This study examined the impact of simultaneous prenatal exposure to both ethanol and nicotine on offspring ethanol preference behaviors and oxytocin system dynamics. Rat dams were given liquid diet (17% ethanol derived calories (EDC)) on gestational day (GD) 5 and 35% EDC from GD 6-20 and concurrently an osmotic minipump delivered nicotine (3-6mg/kg/day) from GD 4-postpartum day 10. Offspring were tested for ethanol preference during adolescence (postnatal day (PND) 30-43) and again at adulthood (PND 60-73), followed by assays for oxytocin mRNA expression and receptor binding in relevant brain regions. Prenatal exposure decreased ethanol preference in males during adolescence, and decreased consumption and preference in females during adulthood compared to controls. Oxytocin receptor binding in the nucleus accumbens and hippocampus was increased in adult prenatally exposed males only. Prenatal exposure to these drugs sex-specifically decreased ethanol preference behavior in offspring unlike reports for either drug separately. The possible role of oxytocin in reduction of ethanol consumption behavior is highlighted.
尽管已知孕期饮酒和吸烟会对胎儿产生不良影响，但孕期饮酒和吸烟的情况仍很常见。每种药物单独的致畸性已得到充分证实；然而，在临床前模型中，同时接触乙醇和尼古丁的影响仍不清楚。本研究考察了产前同时接触乙醇和尼古丁对后代乙醇偏好行为和催产素系统动态的影响。在妊娠第5天，给大鼠母鼠提供液体饮食（17%乙醇热量（EDC）），从妊娠第6天至第20天提供35% EDC，同时从妊娠第4天至产后第10天通过渗透微型泵给予尼古丁（3 - 6mg/kg/天）。在青春期（出生后第30 - 43天）和成年期（出生后第60 - 73天）对后代进行乙醇偏好测试，随后检测相关脑区中催产素mRNA表达和受体结合情况。与对照组相比，产前接触在青春期降低了雄性后代的乙醇偏好，在成年期降低了雌性后代的乙醇消耗量和偏好。仅在成年期产前接触药物的雄性后代中，伏隔核和海马体中的催产素受体结合增加。与单独使用这两种药物的报道不同，产前接触这些药物会性别特异性地降低后代的乙醇偏好行为。研究强调了催产素在减少乙醇消费行为中可能发挥的作用。
