Di Giulio A M, Tenconi B, Malosio M L, Vergani L, Bertelli A, Gorio A
Department of Medical Pharmacol, Faculty of Medicine, University of Milan, Italy.
J Neurosci Res. 1995 Nov 1;42(4):479-85. doi: 10.1002/jnr.490420406.
We have previously shown that rat perinatal exposure to morphine causes dopaminergic and met-enkephalin (ME) and substance P (SP) changes in the striatum during the early postnatal period (Tenconi et al.: Int J Dev Neurosci 10: 517 - 526, 1992); in addition it increases the susceptibility to neurotoxic lesions and impairs regenerative capacity of the serotoninergic system (Gorio et al.: J Neurosci Res 34: 462 - 471, 1993). Our study shows that ME and SP levels increase postnatally in several areas of the rat brain, reaching the highest values between 30 and 60 days, after which the peptide content subsides to lower levels. Perinatal exposure to morphine increases such ME and SP levels during the early stages of postnatal life. No effect of morphine on 5-HT and NE is observed, while the dopaminergic system is mainly affected in the mesencephalon. The pre- and postnatal brain expression of synapsin I mRNA is gradually and progressively localized in discrete areas of the brain. In the brain of rats perinatally exposed to morphine, the abundance of synapsin I mRNA expression is markedly reduced. Therefore, perinatal exposure to morphine affects early postnatal synaptic development in the brain as shown by the altered peptidergic and monoaminergic content and by the reduced synapsin I mRNA expression.
我们之前已经表明,大鼠围产期暴露于吗啡会导致出生后早期纹状体中多巴胺能、甲硫氨酸脑啡肽(ME)和P物质(SP)发生变化(Tenconi等人:《国际发育神经科学杂志》10: 517 - 526, 1992);此外,它还会增加对神经毒性损伤的易感性,并损害血清素能系统的再生能力(Gorio等人:《神经科学研究杂志》34: 462 - 471, 1993)。我们的研究表明,ME和SP水平在大鼠脑的几个区域出生后会升高,在30至60天之间达到最高值,之后肽含量会降至较低水平。围产期暴露于吗啡会在出生后早期增加这种ME和SP水平。未观察到吗啡对5 - HT和NE有影响,而多巴胺能系统主要在中脑受到影响。突触素I mRNA的产前和产后脑表达逐渐且渐进地定位于脑的离散区域。在围产期暴露于吗啡的大鼠脑中,突触素I mRNA表达的丰度明显降低。因此,围产期暴露于吗啡会影响出生后早期脑内的突触发育,这表现为肽能和单胺能含量的改变以及突触素I mRNA表达的降低。