Harrison L M, Zadina J E, Banks W A, Kastin A J
VA Medical Center, Research Service (151), New Orleans, LA 70146.
Brain Res Dev Brain Res. 1993 Oct 15;75(2):207-12. doi: 10.1016/0165-3806(93)90025-6.
Morphine and endogenous peptides can alter developmental processes, inducing changes that can endure into adulthood. Morphiceptin binds to mu opiate receptors and to non-opiate sites labeled by Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), an endogenous brain peptide known to modulate opiate effects. Morphine, morphiceptin, Tyr-MIF-1, morphine + Tyr-MIF-1, and morphiceptin+Tyr-MIF-1 (50 micrograms, s.c.) were given to rats during their first week of life. Animals given morphine alone or in combination with Tyr-MIF-1 had significantly lower body weights for the first 3 weeks of life and delayed eye opening on day 16. Rats given morphine had hypersensitive tail flick responses on day 9 while those given morphine + Tyr-MIF-1 were hypersensitive on days 3, 8, and 9. Locomotor, passive avoidance, and rotorod behaviors were not altered by the neonatal treatments. Transport of [125I]Tyr-MIF-1 out of the brain was tested on day 23 and found to be increased by neonatal morphine, an effect that was significantly potentiated by neonatal Tyr-MIF-1. The results indicate that neonatal administration of peptides and opiates can affect later peptide transport across the blood-brain barrier as well as selected developmental characteristics.
吗啡和内源性肽可以改变发育过程，引发能够持续至成年期的变化。吗啡肽与μ阿片受体以及由酪酪肽（酪氨酰-脯氨酰-亮氨酰-甘氨酰胺）标记的非阿片位点结合，酪酪肽是一种已知可调节阿片作用的内源性脑肽。在大鼠出生后的第一周，给它们皮下注射50微克的吗啡、吗啡肽、酪酪肽、吗啡 + 酪酪肽以及吗啡肽 + 酪酪肽。单独给予吗啡或与酪酪肽联合给予的动物在出生后的前三周体重显著较低，且在第16天睁眼延迟。给予吗啡的大鼠在第9天甩尾反应过敏，而给予吗啡 + 酪酪肽的大鼠在第3天、第8天和第9天过敏。新生期处理并未改变大鼠的运动、被动回避和转棒行为。在第23天测试了[125I]酪酪肽从脑内的转运情况，发现新生期给予吗啡可使其增加，新生期给予酪酪肽可显著增强这一效应。结果表明，新生期给予肽和阿片类药物会影响后期肽跨越血脑屏障的转运以及某些发育特征。
