- 作者: Yao-Chang Chiang; Tsai-Wei Hung; Cynthia Wei-Sheng Lee; Jia-Ying Yan; Ing-Kang Ho
- 作者服務機構: Division of Mental Health & Addiction Medicine, Institute of Population Health Sciences, National Health Research Institutes, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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 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.
Conclusions: Animals 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. - 中文關鍵字: --
- 英文關鍵字: --