Chronic in utero buprenorphine exposure causes prolonged respiratory effects in the guinea pig neonate

Our laboratory studies the effects of in utero opioid exposure on the neonate. In this work we test the effects of chronic in utero exposure to buprenorphine on the neonate. Buprenorphine is a promising candidate for treatment of opioid addiction during pregnancy and it has been suggested to decrease the neonatal abstinence syndrome in human infants. In our guinea pig model, we focused not only on the respiratory effects of in utero exposure on the neonate, but also studied withdrawal signs in the neonate, a major concern of all opioid treatment during pregnancy. Pregnant guinea pigs were treated with daily subcutaneous injections of 0.1 mg/kg buprenorphine during the second half of gestation. We measured weight, locomotor activity and respiratory function in pups of ages 3 to 14 days. Respiratory response was recorded using a two-chamber plethysmograph, while pups were breathing either room air or 5% CO2. Our results show that chronic in utero exposure to buprenorphine induces respiratory effects up to day 14 after birth, while earlier studies have shown that effects of either in utero methadone or morphine only persist in the first week after birth in the guinea pig model. These data provide important information for clinical trials of buprenorphine treatment suggesting that duration and severity of respiratory effects of in utero buprenorphine exposure should be monitored.