Meyer Jerrold S, Grande Mark, Johnson Kenneth, Ali Syed F
Department of Psychology, Neuroscience and Behavior Program, University of Massachusetts, Tobin Hall, 135 Hicks Way, Amherst, MA 01003, USA.
Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):261-71. doi: 10.1016/j.ijdevneu.2004.04.007.
3,4-methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2h after each of twice-daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1-4. Other drug-treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase-3 at postnatal day 5. The hippocampus showed significant MDMA-related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter-immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate-putamen and nucleus accumbens shell. MDMA treatment also produced a two-fold increase in the number of cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long-term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA-using women may be at heightened risk for abnormal neural and behavioral development.
3,4-亚甲基二氧甲基苯丙胺会损害成年生物体中精细的5-羟色胺能纤维和神经末梢。发育中的动物似乎对此效应不太敏感，这可能是由于缺乏药物诱导的体温过高。我们通过在出生后第1至4天每天两次皮下注射摇头丸（10毫克/千克）或生理盐水后，使新生大鼠体温过高2小时来验证这一假设。其他药物处理组和对照组的幼崽在注射后保持正常体温。在出生后第25天（5-羟色胺转运体结合和5-羟色胺水平）、出生后第60天（5-羟色胺转运体结合）和9个月大时（5-羟色胺转运体免疫组织化学）评估前脑5-羟色胺能神经支配的变化。我们还通过在出生后第5天对裂解的半胱天冬酶-3进行免疫组织化学检测，确定了摇头丸处理对凋亡活性的影响。在出生后第25天和第60天，海马体中与摇头丸相关的5-羟色胺能标记物显著减少。在9个月时，先前接触摇头丸对海马体中5-羟色胺转运体免疫反应性纤维密度没有影响；然而，在两个新皮质区域观察到纤维密度显著降低，并且在尾状核-壳核和伏隔核壳中发现了神经支配过度。摇头丸处理还使前脑嘴侧和海马体中裂解的半胱天冬酶-3免疫反应性细胞数量增加了两倍。所有这些效应都与幼崽体温完全无关。这些发现表明，新生期接触摇头丸会刺激前脑各个区域的凋亡细胞死亡，还会导致前脑5-羟色胺能神经支配的长期重组。因此，使用摇头丸的女性的后代可能面临神经和行为发育异常的风险增加。
