title: Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring.
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.
authors.affiliation: Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan. yaochang.chiang@gmail.com.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. yaochang.chiang@gmail.com.
authors.forename: Yao-Chang
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. h76106@hotmail.com.
authors.forename: Li-Ci
authors.initials: LC
authors.lastname: Ye
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. betterin@nhri.org.tw.
authors.forename: Kuei-Ying
authors.initials: KY
authors.lastname: Hsu
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. hawkjwl@gmail.com.
authors.forename: Chien-Wei
authors.initials: CW
authors.lastname: Liao
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. pilypily@nhri.org.tw.
authors.forename: Tsai-Wei
authors.initials: TW
authors.lastname: Hung
authors.affiliation: Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. 0920320319@yahoo.com.tw.
authors.forename: Wan-Jou
authors.initials: WJ
authors.lastname: Lo
authors.affiliation: Center for Drug Abuse and Addiction, China Medical University Hospital, Taichung, Taiwan. iho@mail.cmuh.org.tw.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan. iho@mail.cmuh.org.tw.
authors.forename: Ing-Kang
authors.initials: IK
authors.lastname: Ho
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan. pltao@nhri.org.tw.|Center for Neuropsychiatric Research, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. pltao@nhri.org.tw.
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
mesh_terms: D000818:Animals; D000996:Antitussive Agents / Q000627:therapeutic use*; D003915:Dextromethorphan / Q000627:therapeutic use*; D005260:Female; D008297:Male; D008691:Methadone / Q000008:administration & dosage* / Q000633:toxicity; D009021:Morphine Dependence / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009294:Narcotics / Q000008:administration & dosage* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000996:Antitussive Agents; D009294:Narcotics; D003915:Dextromethorphan; D008691:Methadone