Department of Pediatrics, Division of Neonatology, University of Minnesota, Minneapolis, Minnesota, USA.
J Neurosci Res. 2012 Jan;90(1):307-14. doi: 10.1002/jnr.22750. Epub 2011 Oct 4.
Morphine is frequently used as an analgesic and sedative in preterm infants. Adult rats exposed to morphine have an altered hippocampal neurochemical profile and decreased neurogenesis in the dentate gyrus of the hippocampus. To evaluate whether neonatal rats are similarly affected, rat pups were injected twice daily with 2 mg/kg morphine or normal saline from postnatal days 3 to 7. On postnatal day 8, the hippocampal neurochemical profile was determined using in vivo (1)H NMR spectroscopy. The mRNA and protein concentrations of specific analytes were measured in hippocampus, and cell division in dentate gyrus was assessed using bromodeoxyuridine. The concentrations of γ-aminobutyric acid (GABA), taurine, and myo-insotol were decreased, whereas concentrations of glutathione, phosphoethanolamine, and choline-containing compounds were increased in morphine-exposed rats relative to control rats. Morphine decreased glutamic acid decarboxylase enzyme levels and myelin basic protein mRNA expression in the hippocampus. Bromodeoxyuridine labeling in the dentate gyrus was decreased by 60-70% in morphine-exposed rats. These results suggest that recurrent morphine administration during brain development alters hippocampal structure.
吗啡常被用作早产儿的镇痛和镇静剂。暴露于吗啡的成年大鼠其海马神经化学特征发生改变，海马齿状回的神经发生减少。为了评估新生儿大鼠是否受到类似影响，在出生后 3 至 7 天期间，每日两次给新生大鼠注射 2mg/kg 吗啡或生理盐水。在出生后第 8 天，通过体内（1）H NMR 光谱法测定海马的神经化学特征。在海马中测量特定分析物的 mRNA 和蛋白浓度，并使用溴脱氧尿苷评估齿状回的细胞分裂。与对照组相比，吗啡暴露组大鼠的γ-氨基丁酸（GABA）、牛磺酸和肌醇的浓度降低，而谷胱甘肽、磷酸乙醇胺和含胆碱化合物的浓度升高。吗啡降低了海马中的谷氨酸脱羧酶酶水平和髓鞘碱性蛋白 mRNA 的表达。在吗啡暴露组大鼠的齿状回中，溴脱氧尿苷标记减少了 60-70%。这些结果表明，在大脑发育过程中反复给予吗啡会改变海马结构。
