Abstract
BackgroundHeroin 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.ResultsPrenatal 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-015-0126-2) contains supplementary material, which is available to authorized users.
Highlights
Heroin use among young women of reproductive age has drawn much attention around the world
No matter what these findings provided, a concept that an investigation of possible strategies for reducing the dosage of methadone of maternal use or using a combination of some medicine may be helpful in decreasing adverse effects on offspring that were prenatally exposed to methadone
The body weights of all tested groups at p14 (F(3,28) = 0.47; p = 0.71), p30 (F(3,34) = 2.30; p = 0.09), and p60 (F(3,34) = 0.006; p = 0.999) showed no significant difference (Figure 1B). These results indicate that prenatal exposure to methadone, DM, or methadone + DM at the doses in the current study did not change the survival or growth rate of offspring
Summary
Heroin use among young women of reproductive age has drawn much attention around the world. Several studies suggested that the score of NAS, percentage of treatment for withdrawal, and duration of neonatal hospitalization were positively associated with maternal methadone dosage [18,19,20] This may indicate that higher maternal methadone doses cause severe NAS. The issue of maternal methadone dose versus the prognosis of NAS remain unresolved, that may due to the inability to appropriately control for numerous confusing factors, such as the health status, personal neglect, poor antenatal care [13] No matter what these findings provided, a concept that an investigation of possible strategies for reducing the dosage of methadone of maternal use or using a combination of some medicine may be helpful in decreasing adverse effects (mortality, weight gain, or NAS etc.) on offspring that were prenatally exposed to methadone
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