Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission

Kazuhiro Nishii, Natsuki Matsushita, Hirohide Sawada, Hiromi Sano, Yukihiro Noda, Takayoshi Mamiya, Toshitaka Nabeshima, Ikuko Nagatsu, Tadayoshi Hata, Kazutoshi Kiuchi, Hideo Yoshizato, Kunio Nakashima, Toshiharu Nagatsu, Kazuto Kobayashi

研究成果: ジャーナルへの寄稿学術論文査読

45 被引用数 (Scopus)


Mice lacking expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme of the catecholamine biosynthetic pathway, in dopaminergic neuronal cell types were generated by a transgenic rescue approach to clarify the role of dopamine signaling during postnatal development. Introduction of the TH transgene directed by the dopamine β- hydroxylase gene promoter into TH knockout mice restored noradrenaline and adrenaline synthesis, preventing perinatal lethality and cardiac dysfunction in the knockout mice. Lack of TH expression in the cells that normally express the dopaminergic phenotype resulted in a marked reduction of dopamine accumulation in the tissues, which led to multiple behavioral abnormalities at the juvenile stage. These abnormalities were characterized by a reduction in spontaneous locomotor activity, blockade of methamphetamine-induced hyperactivity, cataleptic behavior, and defects in active avoidance learning. In contrast, development of the pituitary gland as well as production and secretion of the pituitary peptide hormones dependent on hypothalamic dopaminergic control were normally maintained, despite defective dopamine synthesis. These results demonstrate that dopamine neurotransmission is essential for controlling spontaneous and voluntary movement and associative learning during postnatal development through the nigrostriatal and mesocorticolimbic pathways.

ジャーナルJournal of Neuroscience Research
出版ステータス出版済み - 15-11-1998

All Science Journal Classification (ASJC) codes

  • 細胞および分子神経科学


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