Defects induced by prenatal buprenorphine exposure and preventive effects of dextromethorphan

P Tao1,2, Y Yang2, K Hsu1. 1National Health Research Institutes, Division of Mental Health and Addiction Medicine, 350, Taiwan, 2National Defense Medical Center, Graduate Institute of Life Science, 114, Taiwan

Buprenorphine (BUP) maintenance therapy has been adopted to treat heroin addicts for almost 10 years, but there is little information on effects of BUP on their offspring if these female addicts are under BUP maintenance therapy. In this study, an animal model has been established to study effects of prenatal BUP exposure and the preventive effects of dextromethorphan (DM, a non-competitive NMDA antagonist). Female pregnant SD rats were sub-grouped to receive (1) vehicle (2) BUP (3 mg/kg) (3) DM (3 mg/kg) (4) BUP+DM, subcutaneously, once a day from E3 to E20. The natural withdrawal, survival rate, body weight, pain threshold (measured by tail flick test and hot plate test), rewarding (determined by conditioned place preference), behavioral sensitization (determined by locomotion activity), learning and memory (determined by water maze test), etc. were determined in the offspring. We found that prenatal exposure to BUP induced significant natural withdrawal within 24 hours after birth and decreased the survival rate in 7 days after birth. It decreased the body weight of male offspring on p1, p7 and p14 but not on p30 and p60. It increased the pain threshold of male offspring all the way from young (p14) to adult (p60) rats. Prenatal exposure of BUP did not affect learning and memory (by water maze test) or behavioral sensitization but significantly increased the rewarding effect induced by BUP (0.3 mg/kg, 6 conditionings) in the male offspring. Co-administration of DM with BUP during pregnancy reversed (i.e. prevented) most of the above mentioned defects induced by BUP.

Conclusion: Dextromethorphan has potential to prevent the possible defects induced by prenatal exposure of chronic buprenorphine treatment.