Rothe T, Langer M
Paul Flechsig Institute for Brain Research, Department of Neurochemistry, Karl Marx University, Leipzig, G.D.R.
J Neurochem. 1988 Nov;51(5):1361-6. doi: 10.1111/j.1471-4159.1988.tb01098.x.
The postnatal development of [3H]dihydroalprenolol binding to beta-adrenergic receptors has been studied in frontal cortex, cerebellum, striatum, and hypothalamus of the rat after prenatal and perinatal exposure to diazepam. Dams were injected subcutaneously with single daily doses of 1 mg of diazepam/kg from day 7 to 20 of gestation or from day 15 of gestation to day 6 after birth. Prenatal exposure had no effect on litter size or length of gestation or on the postnatal development of body and brain weights of the progeny. However, a reduced mortality of the pups was observed in relation to vehicle-treated controls until postnatal day 10. Prenatal diazepam administration decreased [3H]dihydroalprenolol binding in frontal cortex, striatum, and hypothalamus but not in cerebellum. This decrease in beta-adrenergic receptor binding was due to a decrease in receptor density rather than in receptor affinity. In contrast, perinatal diazepam exposure led to a transient decrease in [3H]dihydroalprenolol binding limited to the frontal cortex. The permanent reduction in number of beta-adrenergic receptors, which depends on the scaling and duration of the drug application period, points to the necessity of a prolonged evaluation of effects of exposure to psychotropic drugs in early stages of brain development.
在大鼠的额叶皮质、小脑、纹状体和下丘脑，研究了产前和围产期暴露于地西泮后[3H]二氢烯丙洛尔与β-肾上腺素能受体结合的产后发育情况。从妊娠第7天至20天或从妊娠第15天至出生后第6天，给孕鼠皮下注射每日单剂量1mg/kg的地西泮。产前暴露对产仔数、妊娠期长度或子代的产后身体和脑重量发育没有影响。然而，与溶剂处理的对照组相比，在出生后第10天之前观察到幼崽死亡率降低。产前给予地西泮会降低额叶皮质、纹状体和下丘脑的[3H]二氢烯丙洛尔结合，但小脑不受影响。β-肾上腺素能受体结合的这种降低是由于受体密度降低而非受体亲和力降低。相比之下，围产期暴露于地西泮导致[3H]二氢烯丙洛尔结合仅在额叶皮质出现短暂降低。β-肾上腺素能受体数量的永久性减少取决于药物应用期的时长和剂量，这表明有必要在脑发育早期对精神药物暴露的影响进行长期评估。
