Walz M A, Davis W M, Pace H B
Dev Pharmacol Ther. 1983;6(2):125-37. doi: 10.1159/000457285.
After 60 days of treating both sexes with daily oral doses of 15 mg/kg methadone hydrochloride, Wistar rats were mated. Drug treatment of females continued until the weaning of their pups. The body weight of pups was reduced compared to controls up to weaning, and viability was significantly decreased. Ontogeny of reflexes was delayed, and exploration in an open-field arena was reduced up to 2 weeks of age, but then increased above controls. Defecation in the open-field arena was lessened. When only the sire received methadone, only the increase in exploratory behavior and the decrease in defecation occurred. Breeding offspring (F1) of which both parents had methadone treatment gave F2 generation offspring for which neonatal mortality was significantly elevated and defecation in the open-field arena was lessened at 21 days. No changes clearly traceable to methadone were found in the subsequent F3 generation. Some F3 generation rats were treated with methadone and bred in the same manner as the original parental generation. The resulting pups, having the genealogy twice-exposed to methadone, were not significantly different from those whose immediate parents only received the drug.
对雌雄Wistar大鼠每日口服15mg/kg盐酸美沙酮60天后进行交配。雌性大鼠的药物治疗持续到幼崽断奶。与对照组相比，幼崽体重在断奶前降低，存活率显著下降。反射发育延迟，在旷场试验中的探索行为在2周龄前减少，但之后高于对照组。旷场试验中的排便减少。当只有父本接受美沙酮时，仅出现探索行为增加和排便减少的情况。双亲都接受美沙酮治疗的繁殖后代（F1）所产生的F2代后代，其新生儿死亡率显著升高，21天时旷场试验中的排便减少。在随后的F3代中未发现明显可追溯到美沙酮的变化。一些F3代大鼠用美沙酮治疗，并以与原始亲代相同的方式繁殖。其谱系两次接触美沙酮的幼崽与那些直接亲本仅接受药物治疗的幼崽没有显著差异。
