Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.
Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.
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DOI：
10.1186/s12929-015-0126-2
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发表时间：
2015-03-20
影响因子：
11
通讯作者：
Tao PL
中科院分区：
文献类型：
--
作者：
Chiang YC;Ye LC;Hsu KY;Liao CW;Hung TW;Lo WJ;Ho IK;Tao PL
育龄年轻妇女使用海洛因的问题在全世界引起了广泛关注。尽管美沙酮被广泛用于海洛因/吗啡成瘾的维持治疗，但产前暴露于美沙酮和预防性治疗的长期影响尚不清楚。为了揭示这一问题，雌性妊娠sd - dawley大鼠分组接受(1)载药，(2)美沙酮在胚胎第3天（E3）为5 mg/kg， E4至E20为7 mg/kg，(3)右美沙芬（DM）为3 mg/kg，(4)美沙酮+ DM（美沙酮后DM治疗），从E3至E20每天皮下注射2次。在子代出生后不同阶段（P1 ~ P79）测定体重、自然戒断、疼痛敏感性、ED50、条件位置偏好和水迷宫。采用实时定量RT-PCR和电生理分别测定脊髓内阿片受体基因表达和海马内LTP/LTD的变化。产前暴露于美沙酮或右美沙芬对后代存活率、体重、水迷宫和LTP或LTD均无影响。然而，产前美沙酮显著增加了戒断症状、疼痛敏感性、成瘾倾向，并降低了疼痛相关阿片受体mRNA的表达。母鼠同时给药美沙酮可有效预防美沙酮所致子代的这些异常。我们的研究清楚地表明，在母鼠中，右美沙芬和美沙酮共同施用可以防止产前美沙酮暴露引起的不良反应。提示右美沙芬与美沙酮联合应用于海洛因成瘾孕妇维持治疗，可预防美沙酮对后代的不良影响。本文的在线版本（doi:10.1186/s12929-015-0126-2）包含补充材料，可供授权用户使用。
Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague–Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately. Prenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone. Our study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring. The online version of this article (doi:10.1186/s12929-015-0126-2) contains supplementary material, which is available to authorized users.