Slamberová R, Hrubá L, Bernásková K, Matejovská I, Rokyta R
Charles University in Prague, Third Faculty of Medicine, Departments of Normal, Pathological and Clinical Physiology, Prague, Czech Republic.
Int J Dev Neurosci. 2010 Oct;28(6):429-35. doi: 10.1016/j.ijdevneu.2010.06.009. Epub 2010 Jun 26.
Stimulant drugs are often associated with increased seizure susceptibility. Inhibitory gamma-aminobutyric acid (GABA) and excitatory N-methyl-D-aspartate (NMDA) systems play a role in the effect of stimulants in the genesis of epileptic seizures. Our previous studies showed that prenatal methamphetamine (MA) exposure induced long-term changes in seizure susceptibility. The aim of the present study was to investigate the effect of cross-fostering on the prenatal and postnatal MA-exposed rats, respectively, on their seizures in adulthood. Bicuculline (GABA(A) receptor antagonist), NMDA (NMDA receptor agonist) and flurothyl (a convulsant gas) were used to induce seizures in adult male offsprings. Female dams were injected with MA (5 mg/kg daily) or physiological saline (S) for approx. 9 week [about 3 week prior to impregnation, for the entire gestation period (22 days) and in preweaning period (21 days)]. Absolute controls (C) did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received pups from all three treatments. Thus, nine groups (based on the prenatal and postnatal drug exposure) of adult male rats were tested in each seizure test: C/C; C/S; C/MA; S/C; S/S; S/MA; MA/C; MA/S; MA/MA. The present study demonstrates that the effect of prenatal and/or postnatal MA exposure is seizure model specific. In addition, our data show that there is an effect of cross-fostering on seizures; particularly, the effect of prenatal MA exposure shown in animals fostered by control mothers is no longer apparent in animals fostered postnatally by MA-treated mothers. Such effect of postnatal treatment is not manifested in prenatal controls. In summary, it seems that: (1) prenatal MA exposure alters seizure susceptibility more than postnatal MA exposure; (2) especially in seizures induced by chemicals that affect GABAergic system (bicuculline, flurothyl) notable effect of adoption (cross-fostering) is apparent; (3) in seizure models that are associated with NMDA system (NMDA, flurothyl), effect of prenatal stress seems to play a role.
兴奋剂类药物通常与癫痫易感性增加有关。抑制性γ-氨基丁酸（GABA）和兴奋性N-甲基-D-天冬氨酸（NMDA）系统在兴奋剂对癫痫发作发生的影响中起作用。我们之前的研究表明，产前暴露于甲基苯丙胺（MA）会导致癫痫易感性的长期变化。本研究的目的是分别研究交叉寄养对产前和产后暴露于MA的大鼠成年后癫痫发作的影响。使用荷包牡丹碱（GABA(A)受体拮抗剂）、NMDA（NMDA受体激动剂）和三氟乙烷（一种惊厥性气体）诱导成年雄性后代癫痫发作。雌性母鼠注射MA（5mg/kg/天）或生理盐水（S）约9周[在受孕前约3周、整个妊娠期（22天）和断奶前期（21天）]。绝对对照组（C）不接受任何注射。在出生后第1天，对幼崽进行交叉寄养，使每只母鼠都接收来自所有三种处理的幼崽。因此，在每次癫痫发作测试中对九组（基于产前和产后药物暴露）成年雄性大鼠进行了测试：C/C；C/S；C/MA；S/C；S/S；S/MA；MA/C；MA/S；MA/MA。本研究表明，产前和/或产后暴露于MA的影响具有癫痫发作模型特异性。此外，我们的数据表明交叉寄养对癫痫发作有影响；特别是，由对照母鼠寄养的动物中显示的产前MA暴露影响在产后由MA处理的母鼠寄养的动物中不再明显。产后处理的这种影响在产前对照组中未表现出来。总之，似乎：（1）产前MA暴露比产后MA暴露更能改变癫痫易感性；（2）特别是在由影响GABA能系统的化学物质（荷包牡丹碱、三氟乙烷）诱导的癫痫发作中，寄养（交叉寄养）的显著影响很明显；（3）在与NMDA系统相关的癫痫发作模型（NMDA、三氟乙烷）中，产前应激的影响似乎起作用。
