Effects of Methadone Exposure during Development on Avian Brain and Blood Cells

Maintenance with methadone is standard treatment for opioid-addicted patients, including pregnant women. Cellular effects of methadone exposure during development are investigated by using an avian model, which is free of confounding maternal variables. In the first study, which explored dose by duration interactions, methadone was administered at one of two doses (0.458 mg/kg or 1.75 mg/kg) for one of three durations of exposure: late in development (Incubation Days 12 to 19), middle to late (Days 9 to 19), or early to late (Days 5 to 19). In the second study, 1.00 mg/kg of methadone was administered from days 8 to 18 and compared with controls (0.00 mg/kg). Brain tissue and blood samples were harvested for all dose conditions from the two studies. Increased methadone exposure was associated with subependymal anomalies, subependymal hemorrhaging, edema, monocytic infiltration, an increase in disintegrating red blood cells, an increase in white blood cells, and a decrease in neurons. Significant differences in variance for cell counts by condition were observed. Exposed specimens had significantly more thrombocytes (t = - 2.66, p < 0.05). The anomalies suggest that methadone exposure may be harmful to develop organisms at the cellular level.