van Veldhuizen M J, Feenstra M G, Botterblom M H, Boer G J
Graduate School Neurosciences, Amsterdam, Netherlands Institute for Brain Research.
Brain Res. 1994 May 16;646(1):19-25. doi: 10.1016/0006-8993(94)90053-1.
Direct and persistent effects of chronic neonatal administration of the beta-adrenoceptor antagonist propranolol on brain noradrenergic activity were investigated by measuring tissue concentrations of noradrenaline and its metabolites and in vivo overflow of noradrenaline during adulthood. Rat pups were chronically treated with propranolol from postnatal day 1 to day 10. Determination of monoamine metabolism after the last injection showed an increase in noradrenaline metabolism in frontal cortex, limbic system and hippocampus of propranolol-exposed rats, but 47 days after this last injection it was apparent that these effects were not long-lasting. Moreover, basal noradrenaline overflow in vivo in the hippocampus of 40-55 day-old propranolol-exposed rats did not differ from that in controls. However, the regulation of noradrenaline release seemed to have been altered, since a pharmacological challenge with the alpha 2-adrenoceptor antagonist idazoxan induced an enhanced increase in the in vivo noradrenaline overflow in propranolol-exposed rats compared to controls. It is suggested that the neonatal beta-blockade induced a supersensitivity of the presynaptic alpha 2-adrenoceptor. The precise mechanism underlying this effect has to be elucidated.
通过测量成年期去甲肾上腺素及其代谢物的组织浓度以及去甲肾上腺素的体内溢出量，研究了长期新生期给予β-肾上腺素能受体拮抗剂普萘洛尔对脑去甲肾上腺素能活性的直接和持续影响。从出生后第1天到第10天，对幼鼠进行普萘洛尔长期治疗。最后一次注射后对单胺代谢的测定显示，暴露于普萘洛尔的大鼠额叶皮质、边缘系统和海马体中的去甲肾上腺素代谢增加，但在最后一次注射47天后，很明显这些影响并非持久。此外，40 - 55日龄暴露于普萘洛尔的大鼠海马体中去甲肾上腺素的基础体内溢出量与对照组没有差异。然而，去甲肾上腺素释放的调节似乎已经改变，因为与对照组相比，用α2-肾上腺素能受体拮抗剂咪唑克生进行药理学刺激后，暴露于普萘洛尔的大鼠体内去甲肾上腺素溢出量的增加更为明显。提示新生期β受体阻断诱导了突触前α2-肾上腺素能受体的超敏反应。这种效应的精确机制有待阐明。
