Respiratory effects of chronic in utero methadone or morphine exposure in the neonatal guinea pig

This study uses a menoatal guinea pig model to compare the effects of in utero methadone or morphine exposure upn breathing control. We hypothesize that in utero methadone exposure will result in similar respiratory disturbances to those seen in morphine exposed neonates, but that the onset will be slower and the duration longer, due to methadone's longer elimination half-life, Pregnant Dunkin-Hartley guinea pigs received once-daily injections of methadone, morphine, or vehicle (saline) during the last half of gestation and pups were studied 3, 7, or 14 days after birth. In utero methadone or morphine exposure resulted in decreased birth weight compared to vehicle and pups experienced a withdrawl syndrome which included increased locomotor activity and respiratory disturbances but no change in rectal temperature. Both opioid exposures increased inspiratory minute ventilation during CO2 challenge at 3 days after birth, but only in morphine exposed pups was this withdrawl effect still present on day 7. Surprisingly only morphone exposure increased inspiratory minute ventilatiion during room air breathing. We conclude that in utero methadone exposure is not equivalent to in utero morphine exposure. With respect to neonatal respiratory control, methadone-induced changes in respiration are only apparent during hypercapnia. (C) 2008 Elsevier Inc. All rights reserved.