PRENATAL ADMINISTRATION OF METHADONE USING THE OSMOTIC MINIPUMP - EFFECTS ON MATERNAL AND OFFSPRING TOXICITY, GROWTH, AND BEHAVIOR IN THE RAT

Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence.