In utero exposure to methadone produces a stable decrease of the cortex 5-HT transport system in rats

Female rats were made dependent to high doses of morphine (400 mg/kg per day) or methadone (60-80 mg/kg per day) and subsequently exposed to adult males. None of the morphine-dependent rats became pregnant while there were no differences in the gestation time and number of young in the litter born to each rat in the methadone and the control groups. The values for muscarinic, serotonergic and opiate receptors measured in the whole brain of the offspring at 1 and 7 days after birth were similar in the control and in the methadone-exposed animals. Brain beta-receptors were lower in rats exposed in utero to methadone at 1 and 7 days. [3H]IMI binding sites were steadily and significantly lower in the whole brain of rats born to methadone-dependent animals than in the brain of controls. In 2 month old animals, the decrease of [3H]IMI binding capacity was associated with a decrease of [3H]5HT uptake. In the light of these findings the authors propose a unifying hypothesis to explain the altered reactivity to morphine of animals treated with opiates during gestation.