Effects of opiates on fetal behavioral activity in utero

Abstract The effects of methadone and morphine on fetal behavior were studied following their administration to either the mother (5ug/kg/min) or fetus (0.5ug/kg maternal wt./min) using the chronically-instrumented pregnant ewe model. Fourteen unanesthetized, unrestrained pregnant ewes between 130–141 days gestation (term 145 days) were studied 9–28 days following the surgical implantation of cannulae and electrodes to monitor fetal heart rate, blood pressure, breathing movements, eye movements, muscular and electrocortical activity. The three behavioral states of quiet sleep, rapid eye movement sleep and arousal could be distinguished using these parameters. Both drugs, by both routes, resulted in fetal arousal, largely at the expense of quiet sleep. While morphine and methadone were equipotent in suppressing quiet sleep following infusion to the fetus, methadone was three times more potent than morphine after maternal infusion. This potency difference is consistent with the results of prior pharmacokinetic studies demonstrating that fetal exposure to maternally administered methadone is approximately three times greater than that to maternally administered morphine.