Enhancement of tolerance development to morphine in rats prenatally exposed to morphine, methadone, and buprenorphine

Journal of Biomedical Science

Research

Ing-Kang Ho¹  Cynthia Wei-Sheng Lee¹  Jia-Ying Yan¹  Tsai-Wei Hung¹  Yao-Chang Chiang¹ 

[1] Division of Mental Health & Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, 35053, Zhunan, Miaoli County, Taiwan ROC;

关键词: Morphine;    Buprenorphine;    Antinociceptive Effect;    Prenatal Exposure;    Methadone Maintenance Treatment;   

DOI  :  10.1186/1423-0127-17-46

 received in 2010-04-01, accepted in 2010-06-07,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAbuse of addictive substances is a serious problem that has a significant impact on areas such as health, the economy, and public safety. Heroin use among young women of reproductive age has drawn much attention around the world. However, there is a lack of information on effects of prenatal exposure to opioids on their offspring. In this study, an animal model was established to study effects of prenatal exposure to opioids on offspring.MethodsFemale pregnant Sprague-Dawley rats were sub-grouped to receive (1) vehicle, (2) 2-4 mg/kg morphine (1 mg/kg increment per week), (3) 7 mg/kg methadone, and (4) 3 mg/kg buprenorphine, subcutaneously, once or twice a day from E3 to E20. The experiments were conducted on animals 8-12 weeks old and with body weight between 250 and 350 g.ResultsResults showed that prenatal exposure to buprenorphine caused higher mortality than other tested substance groups. Although we observed a significantly lower increase in body weight in all of the opioid-administered dams, the birth weight of the offspring was not altered in all treated groups. Moreover, no obvious behavioral abnormality or body-weight difference was noted during the growing period (8-12 weeks) in all offspring. When the male offspring received morphine injection twice a day for 4 days, the prenatally opioid-exposed rats more quickly developed a tolerance to morphine (as shown by the tail-flick tests), most notably the prenatally buprenorphine-exposed offspring. However, the tolerance development to methadone or buprenorphine was not different in offspring exposed prenatally to methadone or buprenorphine, respectively, when compared with that of the vehicle controlled group. Similar results were also obtained in the female animals.ConclusionsAnimals prenatally exposed to morphine, methadone, or buprenorphine developed tolerance to morphine faster than their controlled mates. In our animal model, prenatal exposure to buprenorphine also resulted in higher mortality and much less sensitivity to morphine-induced antinociception than prenatal exposure to morphine or methadone. This indicates that buprenorphine in higher doses may not be an ideal maintenance drug for treating pregnant women. This study provides a reference in selecting doses for clinical usage in treating pregnant heroin addicts.

【 授权许可】

Unknown   
© Chiang et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.