Dopamine transporter density and behavioral response to methylphenidate in a hyperlocomotor rat model
Dopamine transporter density and behavioral response to methylphenidate in a hyperlocomotor rat model
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DOI：
10.1111/j.1741-4520.2006.00119.x
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发表时间：
2006-09-01
影响因子：
1.3
通讯作者：
Takigawa, Morikuni
中科院分区：
文献类型：
--
作者：
Muneoka, Katsumasa;Kuwagata, Makiko;Takigawa, Morikuni
出生前暴露于5-溴-2 '-脱氧尿苷（BrdU-大鼠）的大鼠表现出多动症活动，使它们成为研究注意缺陷多动障碍（ADHD）的可能有用的动物模型。使用该模型，我们研究了BrdU大鼠的多巴胺转运蛋白（DAT）密度和行为结果，其中一些大鼠还给予哌甲酯，哌甲酯是一种广泛用于治疗ADHD的精神兴奋剂。妊娠大鼠从妊娠第9天到第15天暴露于BrdU。在雄性后代中，在三周龄时定量纹状体不同区域的DAT密度。在7周龄时，在旷场环境中评估运动、饲养和梳理行为，有或没有哌甲酯处理（lmg/kg或4 mg/kg）。结果显示，与对照组相比，BrdU大鼠纹状体DAT密度无显著变化。在旷场环境中检测到BrdU-大鼠的极端过度运动，这种效应在用较低和较高剂量的哌甲酯治疗后加剧。仅在对照动物中观察到较高剂量组的自发活动增加。总之，未成年BrdU-大鼠未检测到终末场中多巴胺能神经元的变性，尽管成年动物在轻度应激环境中表现出多动行为以及对促进多巴胺能神经传递的精神兴奋剂超敏反应。
Rats exposed prenatally to 5-bromo-2 '-deoxyuridine (BrdU-rats) display hyperlocomotive activity, making them a possibly useful animal model for the study of attention deficit hyperactivity disorder (ADHD). Using this model, we investigated dopamine transporter (DAT) density and behavioral outcomes in BrdU-rats, some of which were also administered methylphenidate, a psychostimulant that is widely used for the treatment of ADHD. Pregnant rats were exposed to BrdU from gestational day 9 through 15. In male offspring, DAT densities in different regions of the striatum were quantified at three weeks of age. At seven weeks of age, locomotor, rearing and grooming behaviors were evaluated in an open-field setting, with or without methylphenidate treatment (1 mg/kg or 4 mg/kg). The results revealed no significant changes in striatal DAT densities in BrdU-rats compared with controls. Extreme hyperlocomotion of BrdU-rats was detected in the open-field environment, an effect that was exacerbated following treatment with the lower and higher dose of methylphenidate. Such increase in locomotor activity was observed only with the higher dose in control animals. In summary, degeneration of dopaminergic neurons in the terminal field was not detected in juvenile BrdU-rats, although adult animals displayed hyperactive behavior in a mildly stressful environment as well as hypersensitivity to a psychostimulant that facilitates dopaminergic neurotransmission.