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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

The effects of pain threshold in prenatal drug exposure male offspring. Prenatal exposure to methadone (MD) decreased the pain threshold at different ages (p30 or p60) in male offspring and prenatal co-administration of methadone and dextromethorphan (MD + DM) prevented this effect. Acute heat nociceptive responses were determined by (A) tail-flick test and (B) hot-plate test. Data are presented as mean ± S.E.M. (n ≥ 8). *P < 0.05 and **p < 0.01 when compared to the control group.
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Fig2: The effects of pain threshold in prenatal drug exposure male offspring. Prenatal exposure to methadone (MD) decreased the pain threshold at different ages (p30 or p60) in male offspring and prenatal co-administration of methadone and dextromethorphan (MD + DM) prevented this effect. Acute heat nociceptive responses were determined by (A) tail-flick test and (B) hot-plate test. Data are presented as mean ± S.E.M. (n ≥ 8). *P < 0.05 and **p < 0.01 when compared to the control group.

Mentions: Prenatal methadone-exposure significantly decreased the pain threshold of offspring determined by either tail-flick (Figure 2A) or hot-plate test (Figure 2B) on p30 (F(3,31) = 5.00; p < 0.05) or p60 (F(3,29) = 2.85; p < 0.05). Prenatal exposure to DM did not alter the pain threshold of offspring significantly. However, prenatal exposure of DM in conjunction with methadone from E3-E20, prevented the changes induced by prenatal methadone exposure alone either partially or completely in the tail flick and hot plate tests, respectively.Figure 2


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)

The effects of pain threshold in prenatal drug exposure male offspring. Prenatal exposure to methadone (MD) decreased the pain threshold at different ages (p30 or p60) in male offspring and prenatal co-administration of methadone and dextromethorphan (MD + DM) prevented this effect. Acute heat nociceptive responses were determined by (A) tail-flick test and (B) hot-plate test. Data are presented as mean ± S.E.M. (n ≥ 8). *P < 0.05 and **p < 0.01 when compared to the control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: The effects of pain threshold in prenatal drug exposure male offspring. Prenatal exposure to methadone (MD) decreased the pain threshold at different ages (p30 or p60) in male offspring and prenatal co-administration of methadone and dextromethorphan (MD + DM) prevented this effect. Acute heat nociceptive responses were determined by (A) tail-flick test and (B) hot-plate test. Data are presented as mean ± S.E.M. (n ≥ 8). *P < 0.05 and **p < 0.01 when compared to the control group.
Mentions: Prenatal methadone-exposure significantly decreased the pain threshold of offspring determined by either tail-flick (Figure 2A) or hot-plate test (Figure 2B) on p30 (F(3,31) = 5.00; p < 0.05) or p60 (F(3,29) = 2.85; p < 0.05). Prenatal exposure to DM did not alter the pain threshold of offspring significantly. However, prenatal exposure of DM in conjunction with methadone from E3-E20, prevented the changes induced by prenatal methadone exposure alone either partially or completely in the tail flick and hot plate tests, respectively.Figure 2

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