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Biopsychological study on the compensation mechanism of brain dopaminergic system in animal model of hyperactivity

多动动物模型脑多巴胺能系统补偿机制的生物心理学研究

基本信息

批准号：
11410020
负责人：
IWASAKI Tsuneo
金额：
$ 2.94万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11410020/
关键词：
hyperactivity dopamine compensation nucleus accumbens neurotensin reward microdialysis rat

项目摘要

Treatment of neonatal rats with intracerebral 6-hydroxydopamine produces a marked depletion of brain dopamine (DA) and locomotor hyperactivity during preweaning period. In order to investigate the brain reward system in this animal model of hyperactivity, we tested conditioned place preference (CPP) by methamphetamine (MAP) using a CPP test apparatus. Neonatally DA-lesioned rats showed conditioned preference to MAP compartment to the same extent as control rats, suggesting normal functioning of brain reward system. Biochemical analysis of brain DA levels in the accumbens nucleus which is the terminal area of brain DA system showed that DA concentration in this area was below 30% of control animals, however according to a microdialysis study the extracellular levels of DA was almost equal to that of control animals. This suggests DA system damaged at neonatal period shows compensation in the accumbens nucleus.It has been known that midbrain DA neurons have neurotensin (NT) receptors on their cell bodies. We investigated the effect of intracerebral NT injection on the extracellular levels of DA in the accumbens nucleus. The increase of DA levels induced by NT injection was more remarkable in neonatally DA-lesioned rats. This suggests that NT is involved in compensation mechanism of brain dopaminergic system in animal model of hyperactivity.

新生大鼠脑内注射6-羟基多巴胺后，断奶前脑多巴胺(DA)明显耗竭，运动亢进。为了研究这种多动动物模型的脑奖赏系统，我们用甲基苯丙胺(MAP)的条件性位置偏爱(CPP)测试仪进行了测试。新生DA损毁大鼠表现出与对照大鼠相同程度的条件性偏爱，提示大脑奖赏系统功能正常。脑多巴胺系统的终末区域伏隔核内DA含量的生化分析表明，该区域的DA含量低于对照动物的30%，而根据微透析研究，细胞外DA含量几乎与对照动物持平。这提示在新生期受损的DA系统在伏核中有代偿作用。众所周知，中脑DA神经元胞体上有神经降压素(NT)受体。我们观察了脑内注射NT对伏隔核胞外DA水平的影响。新生鼠注射NT后DA水平升高更为显著。提示NT参与了多动动物模型脑多巴胺能系统的代偿机制。