Melo Pedro, Rodrigues Lorena G, Silva M Carolina, Tavares Maria Amélia
Unit of Neurobehaviour, Institute for Molecular and Cell Biology, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
Ann N Y Acad Sci. 2006 Aug;1074:590-603. doi: 10.1196/annals.1369.058.
In recent years there has been growing use of methamphetamine (METH) by pregnant women, resulting in an increasing number of children exposed prenatally to this drug of abuse. METH is known to be potentially neurotoxic to human adults, but there is minimal information with respect to the consequences of such exposure to the fetus. The purpose of this study was to ascertain external parameters of animal development, as well as neurochemical and immunohistochemical alterations at three key points of retinal development (postnatal day [PND] 7, 14, and 30). Rats of the Wistar strain were used in this experimental model. Pregnant females received a dose of 5 mg/kg body weight per day of METH-HCl in 0.9% saline, from gestational day (GD) 8 to 22. The control group to be used was pair fed and saline injected. Litters were randomly culled at PND 1 to 8 pups. Analysis of maternal body weight gain during pregnancy showed that females treated with METH had lower body weights than control-treated females. The body weight on PND 1, showed that animals treated with METH prenatally had smaller body weights than the control-treated animals and also that females weighed less than males. Prenatal exposure to METH did not alter the retinal levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the male group and the level of dopamine (DA) in both female and male groups when compared with their respective pair fed control groups during the first month of life. Correlating with the neurochemical data, no obvious changes on the localization of TH immunoreactivity in the rat retina at PND 7, 14, and 30 could be detected between control and METH-treated animals. Thus, exposure to METH disrupted this pattern in a gender-dependent manner. These data confirm previous observation that developing rats are protected against the adult type of METH-induced neurotoxicity. Therefore, conventional markers used for adult animals appear to be unsatisfactory to demarcate boundaries of the PND 1 to 30 critical periods.
近年来,孕妇使用甲基苯丙胺(METH)的情况日益增多,导致越来越多的儿童在产前接触到这种滥用药物。已知METH对成年人类具有潜在的神经毒性,但关于这种接触对胎儿的影响的信息却很少。本研究的目的是确定动物发育的外部参数,以及视网膜发育三个关键点(出生后第[PND]7、14和30天)的神经化学和免疫组化改变。本实验模型使用了Wistar品系的大鼠。怀孕的雌性大鼠从妊娠第8天至22天,每天接受剂量为5mg/kg体重的盐酸甲基苯丙胺,溶于0.9%的盐水中。对照组采用配对喂食并注射生理盐水。在出生后第1天至第8天随机挑选幼崽。对孕期母鼠体重增加的分析表明,接受METH治疗的雌性大鼠体重低于接受对照治疗的雌性大鼠。出生后第1天的体重显示,产前接受METH治疗的动物体重比接受对照治疗的动物小,而且雌性比雄性体重轻。与各自的配对喂食对照组相比,产前接触METH在出生后第一个月并未改变雄性组中3,4-二羟基苯乙酸(DOPAC)的视网膜水平以及雌性和雄性组中多巴胺(DA)的水平。与神经化学数据相关联,在出生后第7、14和30天,对照动物和接受METH治疗的动物之间,未检测到大鼠视网膜中酪氨酸羟化酶(TH)免疫反应性定位有明显变化。因此,接触METH以性别依赖的方式破坏了这种模式。这些数据证实了先前的观察结果,即发育中的大鼠对成年型METH诱导的神经毒性具有保护作用。因此,用于成年动物的传统标志物似乎不足以划定出生后第1天至第30天关键期的界限。