Rech R H, Lomuscio G, Algeri S
Neurobehav Toxicol. 1980 Summer;2(2):75-8.
Gravid rats were treated with methadone, 10 mg/kg/day, or vehicle, from day 5 of gestation to term. The offspring were nursed by foster mothers receiving either methadone or vehicle to form 4 groups: (A) methadone during gestation and lactation, (B) methadone during gestation, (C) methadone during lactation, and (D) no drug treatment. Brain monoamines and metabolites were examined at 21 days of age and found to be decreased in groups A and B. Animals treated comparably to group B and sacrificed at 90 days of age showed no abnormalities in brain monoamines excepting a decrease in dopamine metabolites in limbic areas. Another group treated in utero with methadone was tested at 90 days fo age for shuttle-box avoidance acquisition using massed trials. Methadone-exposed subjects exhibited more avoidances, escapes and intertrial shuttles than controls by the third day of training. These results suggest that subtle but lasting changes in limbic dopamine functions as a consequence of fetal exposure to methadone may make rats hyper-responsive in a massed-trial avoidance procedure in the shuttle-box.
妊娠大鼠从妊娠第5天至足月，每天接受10毫克/千克美沙酮或赋形剂治疗。后代由接受美沙酮或赋形剂的代孕母亲哺乳，形成4组：(A)妊娠和哺乳期接受美沙酮，(B)妊娠期间接受美沙酮，(C)哺乳期接受美沙酮，(D)未接受药物治疗。在21日龄时检测脑单胺和代谢产物，发现A组和B组有所减少。与B组接受相同处理并在90日龄处死的动物，除边缘区域多巴胺代谢产物减少外，脑单胺未发现异常。另一组在子宫内接受美沙酮治疗的动物在90日龄时，使用集中训练试验进行穿梭箱回避学习测试。到训练第三天，暴露于美沙酮的受试动物比对照组表现出更多的回避、逃脱和试验间穿梭行为。这些结果表明，胎儿暴露于美沙酮导致边缘多巴胺功能发生细微但持久的变化，可能使大鼠在穿梭箱集中训练试验回避程序中反应过度。
