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Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

Chiang YC, Ye LC, Hsu KY, Liao CW, Hung TW, Lo WJ, Ho IK, Tao PL - J. Biomed. Sci. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan. yaochang.chiang@gmail.com.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Prenatal exposure to methadone did not affect the survival rate and body weight. (A) The survival rate of offspring on day 7 after birth or (B) the body weight at different ages of male offspring. Data are presented as mean ± S.E.M. (n ≥ 8).
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Fig1: Prenatal exposure to methadone did not affect the survival rate and body weight. (A) The survival rate of offspring on day 7 after birth or (B) the body weight at different ages of male offspring. Data are presented as mean ± S.E.M. (n ≥ 8).

Mentions: As shown in Figure 1A, the survival rate of offspring on day 7 after birth for the methadone, DM, and methadone + DM groups did not differ significantly from the control group (F(3,27) = 3.19; p = 0.08). The litter sizes in all tested groups were not significantly different in current study. Similarly, 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.Figure 1


Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.

Chiang YC, Ye LC, Hsu KY, Liao CW, Hung TW, Lo WJ, Ho IK, Tao PL - J. Biomed. Sci. (2015)

Prenatal exposure to methadone did not affect the survival rate and body weight. (A) The survival rate of offspring on day 7 after birth or (B) the body weight at different ages of male offspring. Data are presented as mean ± S.E.M. (n ≥ 8).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4376496&req=5

Fig1: Prenatal exposure to methadone did not affect the survival rate and body weight. (A) The survival rate of offspring on day 7 after birth or (B) the body weight at different ages of male offspring. Data are presented as mean ± S.E.M. (n ≥ 8).
Mentions: As shown in Figure 1A, the survival rate of offspring on day 7 after birth for the methadone, DM, and methadone + DM groups did not differ significantly from the control group (F(3,27) = 3.19; p = 0.08). The litter sizes in all tested groups were not significantly different in current study. Similarly, 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.Figure 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan. yaochang.chiang@gmail.com.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus