Pappas B A, Peters D A, Sobrian A K, Blouin A, Drew B
Pharmacol Biochem Behav. 1975 Jul-Aug;3(4):681-5. doi: 10.1016/0091-3057(75)90192-6.
New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons.
新生大鼠连续7天每天注射6-羟基多巴胺（6-OHDA）或胍乙啶。每隔3天测量一次运动活性，这些药物对其有不同影响，尽管两种药物都未消除运动活性个体发育的特征模式。还观察到不同的神经化学效应。6-OHDA降低了皮质和小脑中酪氨酸羟化酶的活性，增加了脑干中的活性，对下丘脑没有影响。胍乙啶使所有四个脑区的酶水平略有升高，在16日龄时脑干中的升高显著。从1、5或9日龄开始每天注射4次6-OHDA后，脑区酶活性的变化表明6-OHDA对儿茶酚胺能神经元的毒性作用具有年龄依赖性。这些数据无论是从血脑屏障对6-OHDA通透性的成熟变化还是药物的神经元摄取方面都不符合简单的解释。对脑干区域的进一步分析表明，6-OHDA后脑干酶活性的增加仅限于脑桥。
