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尼古丁在整个早期发育过程中的暴露会促进青少年老鼠对尼古丁的自我给药,并引起持久的行为变化。

Nicotine exposure throughout early development promotes nicotine self-administration in adolescent mice and induces long-lasting behavioural changes.

机构信息

Valdman Institute of Pharmacology, Pavlov State Medical University, 6/8 Lev Tolstoy Street, 197022 St. Petersburg, Russia.

出版信息

Eur J Pharmacol. 2010 Aug 25;640(1-3):87-93. doi: 10.1016/j.ejphar.2010.04.044. Epub 2010 May 8.

Abstract

Maternal cigarette smoking during pregnancy can result in behavioural problems of the offspring. Although the causative agent in tobacco smoke that leads to these aberrations is not known, some studies using animal models have supported the hypothesis that nicotine may cause impairments in fatal and neonatal development. However, in many of the animal studies nicotine has been administered by subcutaneous injections, which could lead to significant fetal hypoxia; some routes of drug administration included stressful procedures to pregnant dams that could create unfavorable fetal environment. In this study, mice were exposed to nicotine via drinking solution. The effects of nicotine exposure throughout early development on behavioural measures during adolescence and adulthood were examined. Adult female dams were allowed to orally self-administer a saccharin, or nicotine plus saccharin solution during gestation and lactation. Following weaning, plasma nicotine concentrations were measured in nicotine-exposed dams, and their offspring were tested using various behavioural measures. [3H]Epibatidine binding was also measured in the cortex and hippocampus at two different time points in the nicotine-exposed adolescents. The results of the study indicate that exposure to nicotine throughout early development influenced intravenous nicotine self-administration, social interactions and performance under a forced swim test. Exposure throughout early development to nicotine however did not affect [3H]epibatidine binding in the hippocampus and cortex.

摘要

母亲在怀孕期间吸烟会导致后代出现行为问题。虽然导致这些异常的烟草烟雾中的致病因素尚不清楚,但一些使用动物模型的研究支持了这样一种假设,即尼古丁可能导致胎儿和新生儿发育受损。然而,在许多动物研究中,尼古丁是通过皮下注射给予的,这可能导致胎儿严重缺氧;一些药物给予途径包括对怀孕的母鼠进行有压力的操作,这可能会造成不利于胎儿的环境。在这项研究中,通过饮用溶液使小鼠接触尼古丁。研究了早期发育过程中暴露于尼古丁对青春期和成年期行为测量的影响。成年雌性母鼠在妊娠期和哺乳期被允许口服糖精或尼古丁加糖精溶液。断奶后,测量暴露于尼古丁的母鼠的血浆尼古丁浓度,并使用各种行为测量方法对其后代进行测试。还在两个不同时间点测量了暴露于尼古丁的青少年大脑皮质和海马中的[3H]依匹巴汀结合。该研究的结果表明,早期发育过程中暴露于尼古丁会影响静脉内尼古丁的自我给药、社会互动和强迫游泳试验中的表现。然而,早期发育过程中暴露于尼古丁并不会影响海马体和皮质中的[3H]依匹巴汀结合。

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