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

Abuse 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. Methods: Female 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. | Chiang et al. Journal of Biomedical Science 2010 17 46 http www.jbiomedsci.eom content 17 1 46 a NSC Tha cost of publication In Journal of Blomodlcal Science Is boms by tlM National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Enhancement of tolerance development to morphine in rats prenatally exposed to morphine methadone and buprenorphine Yao-Chang Chiang Tsai-Wei Hung Cynthia Wei-Sheng Lee Jia-Ying Yan and Ing-Kang Ho Abstract Background Abuse 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. Methods Female 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. Results Results 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 .