Department of Pharmacodynamics, Semmelweis University, H-1085, Budapest, Nagyvárad tér 4, Hungary.
Behav Brain Res. 2010 Jan 20;206(2):299-309. doi: 10.1016/j.bbr.2009.09.031. Epub 2009 Sep 24.
The recreational party drug "ecstasy" (3,4-methylenedioxymethamphetamine MDMA) is particularly popular among young adults who are in the childbearing age and thus there is a substantial risk of prenatal MDMA exposure. We applied an intermittent treatment protocol with an early first injection on pregnant Wistar rats (15 mg/kg MDMA s.c. on the E4, E11 and E18 days of gestation) to examine the potential physiological, endocrine and behavioral effects on adult male and female offspring. Prenatal MDMA-treatment provoked reduced body weight of offspring from the birth as far as the adulthood. Adult MDMA-offspring had a reduced blood-glucose concentration and hematocrit, altered relative spleen and thymus weight, had lower performance on wire suspension test and on the first trial of rotarod test. In contrast, no alteration in the locomotor activity was found. Anxiety and depression related behavioral parameters in elevated plus maze, sucrose preference or forced swimming tests were normal. MDMA-offspring had elevated concentration of the ACTH-precursor proopiomelanocortin and male MDMA-offspring exhibited elevated blood corticosterone concentration. No significant alteration was detected in the serotonergic marker tryptophan-hydroxylase and the catcholaminergic marker tyrosine-hydroxylase immunoreactive fiber densities in MDMA-offspring. The mothers exhibited reduced densities of serotonergic but not catecholaminergic fibers after the MDMA treatment. Our findings suggest that an intermittent prenatal MDMA exposure with an early first injection and a relatively low cumulative dose provokes mild but significant alterations in physical-physiological parameters and reduces motor skill learning in adulthood. In contrast, these adult offspring do not produce anxiety or depression like behavior.
娱乐性派对药物“摇头丸”(3,4-亚甲二氧基甲基苯丙胺,MDMA)在处于生育年龄的年轻成年人中特别受欢迎,因此存在胎儿 MDMA 暴露的实质性风险。我们应用了一种间歇性治疗方案,在怀孕的 Wistar 大鼠(在妊娠第 4、11 和 18 天皮下注射 15mg/kg MDMA)中进行了早期首次注射,以检查对成年雄性和雌性后代的潜在生理、内分泌和行为影响。产前 MDMA 治疗导致后代从出生到成年的体重减轻。成年 MDMA 后代的血糖浓度和血细胞比容降低,相对脾脏和胸腺重量改变,在悬线测试和旋转棒测试的第一次试验中表现较差。相比之下,未发现运动活性的改变。在高架十字迷宫、蔗糖偏好或强迫游泳测试中,焦虑和抑郁相关的行为参数正常。MDMA 后代的 ACTH 前体促黑皮质素原浓度升高,雄性 MDMA 后代的血液皮质酮浓度升高。在 MDMA 后代中未检测到 5-羟色胺能标志物色氨酸羟化酶和儿茶酚胺能标志物酪氨酸羟化酶免疫反应纤维密度的显著改变。母亲在接受 MDMA 治疗后,5-羟色胺能纤维但不是儿茶酚胺能纤维的密度降低。我们的研究结果表明,早期首次注射和相对低累积剂量的间歇性产前 MDMA 暴露会引起轻度但显著的生理参数改变,并降低成年后的运动技能学习能力。相比之下,这些成年后代不会产生焦虑或抑郁样行为。