Gorio A, Malosio M L, Vergani L, Di Giulio A M
Laboratory for Research on Pharmacology of Neurodegenerative Disorders, Department of Medical Pharmacology, Milano, Italy.
Int J Dev Neurosci. 1996 Jul;14(4):471-9. doi: 10.1016/0736-5748(95)00106-9.
This study shows that perinatal exposure to morphine promotes developmental changes (up to 8 months of life) in the striatum by up-regulating concentrations of substance P and met-enkephalin with changes of prometenkephalin A mRNA expression at the day of birth only. Dopamine metabolism (up to 60 days) is also increased as suggested by the reduced concentrations of dopamine and increased content of 3,4-dihydroxyphenylacetic acid. Tyrosine hydroxylase mRNA expression is selectively reduced only in the substantia nigra by perinatal morphine. Serotonin content is reduced only during the early postnatal days and is unaffected thereafter. Supplementation of naltrexone to morphine-exposed rats prevents monoaminergic and neuropeptidergic changes in the striatum, which directly implicates opioid receptors in the developmental changes caused by morphine. The data suggest that perinatal morphine may inhibit met-enkephalin release, causing accumulation of the peptide without corresponding changes in specific mRNA. Dopamine release may also be increased as indicated by a higher metabolism and consequent reduction of tyrosine hydroxylase mRNA expression in the substantia nigra.
本研究表明,围产期暴露于吗啡通过仅在出生当天上调P物质和甲硫氨酸脑啡肽的浓度以及前脑啡肽A mRNA表达的变化,促进纹状体的发育变化(直至生命8个月)。多巴胺代谢(直至60天)也增加,这表现为多巴胺浓度降低和3,4-二羟基苯乙酸含量增加。围产期吗啡仅使黑质中的酪氨酸羟化酶mRNA表达选择性降低。血清素含量仅在出生后早期降低,此后不受影响。给暴露于吗啡的大鼠补充纳曲酮可预防纹状体中的单胺能和神经肽能变化,这直接表明阿片受体参与了吗啡引起的发育变化。数据表明,围产期吗啡可能抑制甲硫氨酸脑啡肽的释放,导致该肽的积累,而特定mRNA无相应变化。如较高的代谢以及随之而来的黑质中酪氨酸羟化酶mRNA表达降低所示,多巴胺释放也可能增加。