Background and aim: Few animal studies of opioid maintenance treatment (OMT) during pregnancy  mimic the clinical situation. The doses used have been questioned, due to missing pharmacokinetics, and  exposure time might also be debated. Hence, with this study we aim to establish a treatment protocol in rats more similar to human exposure to examine the effect on the neonatal offspring.
Method: Female rats were implanted with 28-days osmotic minipumps delivering methadone (10 mg/kg/day), buprenorphine (1 mg/kg/day) or sterile water 4 days prior to mating, or during the first week of pregnancy. Opioid concentrations were analyzed in blood from pregnant dams and in blood and brain from newborn pups. Neonatal withdrawal was examined with ultrasonic vocalization (USV) and analysis of corticosterone in blood. 
Results: The maternal blood concentrations of methadone or buprenorphine were comparable to human exposure and stable throughout pregnancy. At postnatal day 1, the administered opioids were present in both blood and brain from the offspring, with highest concentrations in the brain. Pups prenatally exposed to methadone, but not buprenorphine, displayed withdrawal symptoms with increased USV and elevated levels of the stress hormone corticosterone. 
Conclusion: Prenatal exposure to methadone or buprenorphine during pregnancy caused presence of both opioids in blood and brain of newborn offspring. The study also showed that methadone but not buprenorphine caused withdrawal symptoms in the neonates. This could be important to consider when choosing OMT treatment.

06 - THE EFFECT ON NEONATAL RAT OFFSPRING BORN TO DAMS EXPOSED TO METHADONE OR BUPRENORPHINE DURING PREGNANCY