Early administration of tiapride to young rats without long-lasting changes in the development of the dopaminergic system
Early administration of tiapride to young rats without long-lasting changes in the development of the dopaminergic system
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DOI：
10.1055/s-2004-827171
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发表时间：
2004-07-01
影响因子：
4.3
通讯作者：
Rothenberger, A
中科院分区：
文献类型：
--
作者：
Bock, N;Moll, GH;Rothenberger, A
背景：苯甲酰胺噻必利是一种选择性多巴胺D2/ d3受体拮抗剂，可有效治疗儿童抽动障碍和口吃。噻必利是临床上安全的物质（即使在长期治疗期间和给幼儿服用时也是如此）。不幸的是，它对一般大脑发育和多巴胺能系统成熟的可能影响尚未被研究。因此，儿童药物治疗的重要信息缺失。因此，本研究描述了tiapride给药（30 mg/kg/天）后对青春期前（25-39天）和青春期后（50-64天）大鼠多巴胺能活性的几个参数（多巴胺转运体、D2受体、多巴胺、DOPAC和纹状体中的同型香草酸）的影响。方法：三组大鼠（n = 6）连续14 d在饮水中给予噻必利。两组在青春期前治疗；其中一只在第50天被杀，另一只在第90天被杀。青春期后治疗组在第90天进行测量。第四组（n = 6）从第50天至第53天治疗，第53天服用噻必利。通过配体结合试验（[H-3]-GBR结合多巴胺转运体和[H-3]-spiperone结合D2受体的K-D和B-max值）和HPLC（多巴胺、DOPAC和同型香草酸的浓度）测量变化。结果：早期（第25天）和晚期（第50天）给药后，多巴胺转运体和D2受体的密度未受影响。只有在治疗期间，d2受体结合（spiperone的置换）以及多巴胺和DOPAC水平才会显著降低。结论：这些数据表明，产后脑发育期间服用噻必利不会对中枢多巴胺能系统的发育产生长期的影响，这与儿童的临床经验相符。
Background: The benzamide tiapride, a selective dopamine D2/D3-receptor antagonist, can be used effectively in children to treat tic disorders and stuttering. Tiapride is a clinically safe substance (even during long-term treatment and when given to young children). Unfortunately, its probable effects on general brain development and the maturation of the dopaminergic system have not been investigated. Thus, important information for drug treatment in children is missing. Therefore, this study in rats describes tiapride's effects on several parameters of dopaminergic activity (dopamine transporter, D2 receptor, dopamine, DOPAC, and homovanillic acid in the striatum) seen after tiapride administration (30 mg/kg/day) to prepubertal (from day 25-39) and postpubertal (from day 50-64) rats. Methods: Three groups of rats (n = 6) received tiapride within their drinking water for 14 days. Two groups were treated before puberty; one of those was killed at day 50, the other at day 90. The group treated after puberty was measured at day 90. A fourth group (n = 6) was treated from day 50 to day 53 and measured under tiapride at day 53. Changes were measured by ligand-binding assays (K-D and B-max values of dopamine transporter by [H-3]-GBR binding and D2 receptor by [H-3]-spiperone binding) and by HPLC (concentrations of dopamine, DOPAC, and homovanillic acid). Results: The density of dopamine transporters and D2 receptors remained unaffected after early (day 25) and late (day 50) tiapride administration. Only during the treatment period could a significant reduction of D2-receptor binding (displacement of spiperone) and of dopamine and DOPAC levels be stated. Conclusions: These data suggest that tiapride treatment during postnatal brain development causes no long-lasting changes in the development of the central dopaminergic system and is in line with clinical experience in children.