Ford D H, Rhines R K
Acta Neurol Scand. 1979 May;59(5):248-62. doi: 10.1111/j.1600-0404.1979.tb02935.x.
Offspring from methadone-treated Wistar rats (last trimester of pregnancy), as compared to ad lib and pair fed controls, showed a reduction of body growth which continued throughout the 28-day period during which animals were observed after birth. Brain growth, as indicated by weight, cortical thickness and number of cells in the neocortex also showed a reduction in growth, which was apparent only during the first 14 days, after which there were no differences between the groups. However, in the hippocampus, neuronal density changes/unit area continued throughout the 28-day period in the methadone exposed group and to a lesser extent in the PF group suggesting that this area of brain did not return to normal dimensions or degree of maturation by the end of the third week. Since it has been suggested that any deficit in growth associated with prenatalmethadone-exposure might be due to a reduction in food intake, a group pair-fed to the amount of food consumed by the methadone group was included in the study. Generally, the data from the PF group was intermediate between that obtained from the ad lib fed controls and the methadone-exposed animals. Thus, while some of the growth reduction observed in the methadone-exposed pups could have been due to the impaired nutritional status of their mothers during the last third of pregnancy, a part of the reduced growth must be attributed to the drug treatment, since the reduced growth exceeded that observed in the pair-fed group.
与随意进食和配对喂食的对照组相比，孕期最后三个月接受美沙酮治疗的Wistar大鼠所产的后代，其身体生长出现减缓，在出生后的28天观察期内这种减缓一直持续。以重量、皮质厚度和新皮质细胞数量衡量的大脑生长也出现减缓，不过这种减缓仅在出生后的头14天明显，此后各实验组之间并无差异。然而，在海马体中，美沙酮暴露组在整个28天观察期内单位面积的神经元密度持续变化，配对喂食组的变化程度较小，这表明到第三周结束时，大脑的这个区域并未恢复到正常大小或成熟程度。鉴于有观点认为，产前美沙酮暴露导致的生长缺陷可能是由于食物摄入量减少，该研究纳入了一组按美沙酮组的食物消耗量进行配对喂食的大鼠。总体而言，配对喂食组的数据介于随意进食的对照组和美沙酮暴露组之间。因此，虽然在美沙酮暴露的幼崽身上观察到的部分生长减缓可能是由于其母亲在孕期最后三个月营养状况不佳，但部分生长减缓必定归因于药物治疗，因为生长减缓的程度超过了配对喂食组。
