Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity.
Prenatal cocaine administration stimulates fetal brain tyrosine hydroxylase activity.
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产前注射可卡因会刺激胎儿大脑酪氨酸羟化酶活性。
DOI：
10.1016/0006-8993(93)90783-j
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发表时间：
1993
期刊：
影响因子：
2.9
通讯作者：
Dupont,SA
中科院分区：
文献类型：
--
作者：
Meyer,JS;Dupont,SA
产前接触可卡因的功能影响可能部分是由儿茶酚胺能发育的变化介导的。本研究检查了可卡因的施用是否影响胎儿脑中酪氨酸羟化酶（TH）的活性，酪氨酸羟化酶是儿茶酚胺生物合成中的限速酶。从妊娠第 8 天到妊娠第 20 天，每天给妊娠大鼠皮下 (s.c.) 注射 40 mg/kg 盐酸可卡因，与对照组相比，对胎儿全脑 TH 活性产生了 8.7% 的刺激。然后我们换到了 s.c.。植入过程涉及填充有 80 毫克溶解在聚乙二醇 (PEG) 中的可卡因碱的硅橡胶胶囊。在 GD18 上植入 2 个这样的胶囊，仅 3 天后在 GD21 上测量，胎儿 TH 活性增加了 28%。随后的实验表明，GD14 植入在刺激 GD17 上的胎儿 TH 活性方面同样有效，但该酶在接受治疗的母鼠大脑中不受影响。当在 GD18 时植入含有可卡因的胶囊，在 GD21 时取出，并且允许雌性正常分娩时，后代 TH 活性在出生后第 10 天（但不是更晚）仍然升高。最后，从 GD18 到 GD21，可卡因植入物的存在对胎儿大脑神经递质和代谢物浓度没有影响，然而，接受治疗的母鼠多巴胺 (DA) 和血清素代谢物 5-羟基吲哚乙酸显着减少。我们得出的结论是，母体可卡因植入快速但短暂地刺激胎儿大脑中的 TH 活性，并且这种刺激阻止了在母鼠中观察到的 DA 消耗。
Functional effects of prenatal cocaine exposure may be mediated in part by changes in catecholaminergic development. The present study examined whether cocaine administration influenced fetal brain activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis. Subcutaneous (s.c.) injection of pregnant rats with 40 mg/kg of cocaine HCl daily from gestational day (GD) 8 to GD20 resulted in an 8.7% stimulation of fetal whole-brain TH activity compared to controls. We then switched to a s.c. implantation procedure involving Silastic capsules filled with 80 mg of cocaine base dissolved in polyethylene glycol (PEG). Implantation of 2 such capsules on GD18 produced a 28% increase in fetal TH activity measured only 3 days later on GD21. Subsequent experiments demonstrated that GD14 implantation was equally effective in stimulating fetal TH activity on GD17, but that the enzyme was unaffected in the brains of the treated dams. When cocaine-containing capsules were implanted on GD18, removed on GD21, and the females were allowed to deliver normally, offspring TH activity was still elevated on postnatal day 10 but not later. Finally, the presence of cocaine implants from GD18 to GD21 had no influence on fetal brain neurotransmitter and metabolite concentrations, however, the treated dams exhibited significant reductions in dopamine (DA) and the serotonin metabolite, 5-hydroxyindoleacetic acid. We conclude that maternal cocaine implants rapidly but transiently stimulate TH activity in the fetal brain, and that such stimulation prevented the DA depletion observed in the dams.