Shaywitz B A, Klopper J H, Gordon J W
Arch Neurol. 1978 Jul;35(7):463-9. doi: 10.1001/archneur.1978.00500310065014.
In order to better devine the relationship between brain catecholaminergic mechanisms and the clinical syndrome of minimal brain dysfunction, we have developed an experimental model that has many of the features of the disorder seen in children. This model is effected by the preferential depletion of brain dopamine in 5-day-old rat pups following the intracisternal administration of 6-hydroxydopamine, and in the present investigation, we have examined the effects of methylphenidate hydrochloride (0.25 to 2.0 mg/kg) on activity levels and cognitive performance in normal and 6-hydroxydopamine treated animals. Methylphenidate therapy resulted in a significant increase in activity levels of normal rat pups 12 and 19 days of age; in contrast, methylphenidate administered to 6-hydroxydopamine-treated animals did not increase activity at 12 days of age and significantly reduced activity at 19 and 26 days. Methylphenidate had no effect on T-maze performance in normals, but significantly improved performance in 6-hydroxydopamine-treated animals. Our results suggest that the "paradoxical" response to methylphenidate found in 6-hydroxydopamine-treated rat pups may be the result of central denervation supersensitivity.
为了更好地探究脑内儿茶酚胺能机制与小儿轻微脑功能障碍临床综合征之间的关系，我们建立了一种实验模型，该模型具有许多儿童所患该疾病的特征。此模型通过向5日龄幼鼠脑池内注射6-羟基多巴胺，优先耗竭脑内多巴胺来实现。在本研究中，我们检测了盐酸哌甲酯（0.25至2.0毫克/千克）对正常及经6-羟基多巴胺处理的动物的活动水平和认知表现的影响。哌甲酯治疗使12日龄和19日龄正常幼鼠的活动水平显著增加；相比之下，给经6-羟基多巴胺处理的动物注射哌甲酯，在12日龄时并未增加其活动，而在19日龄和26日龄时显著降低了活动水平。哌甲酯对正常动物的T迷宫表现没有影响，但显著改善了经6-羟基多巴胺处理的动物的表现。我们的结果表明，在经6-羟基多巴胺处理的幼鼠中发现的对哌甲酯的“矛盾”反应可能是中枢去神经超敏反应的结果。
