Slotkin T A, Lau C, Bartolomé M
J Pharmacol Exp Ther. 1976 Oct;199(1):141-8.
Methadone was administered daily to pregnant or nursing rats, or directly to neonates, and the effects on brain and heart weights and ornithine decarboxylase (ODC) activities were determined during postnatal development. Exposure to methadone in the postnatal period either directly or via the mother resulted in delays in maturational decreases in brain ODC accompanied by deficits in brain weight. Prenatal exposure alone had less effect on brain weight or ODC but appeared to enhance the effect of subsequent methadone exposure during the postnatal period. In the heart, direct methadone exposure or prenatal plus postnatal maternal administration led to a pattern of altered ODC activity consistent with delayed development, accompanied by heart weight deficits. The disturbance of heart ODC development after purely prenatal or purely postnatal maternal exposures differed from that obtained after direct administration to the neonate. These data show that exposure to methadone during fetal and/or neonatal life produces alterations in polyamine metabolism which may result in abnormal organ development. The type of change is dependent upon the period and route of exposure and may reflect both direct effects on the pup and indirect effect from drug-induced alterations in maternal metabolism or behavior.
每天给怀孕或哺乳的大鼠服用美沙酮,或直接给新生大鼠服用,然后在产后发育期间测定对脑重、心脏重量和鸟氨酸脱羧酶(ODC)活性的影响。在产后期间直接或通过母体接触美沙酮会导致脑ODC成熟性降低延迟,并伴有脑重量不足。仅产前接触对脑重量或ODC的影响较小,但似乎会增强产后期间后续美沙酮接触的影响。在心脏方面,直接接触美沙酮或产前加产后母体给药会导致ODC活性改变,与发育延迟一致,并伴有心脏重量不足。单纯产前或单纯产后母体接触后心脏ODC发育的紊乱与直接给新生大鼠给药后不同。这些数据表明,在胎儿和/或新生儿期接触美沙酮会导致多胺代谢改变,这可能导致器官发育异常。变化的类型取决于接触的时期和途径,可能反映了对幼崽的直接影响以及药物引起的母体代谢或行为改变的间接影响。