Dopamine deficiency in mice.
Dopamine is the principal neurotransmitter that mediates a wide range of brain functions, including locomotion, emotion, learning, and neuroendocrine modulation. To clarify the role of dopamine during postnatal development, it is useful to have mutant mice genetically deleting dopamine. In this paper, we describe the mice lacking expression of tyrosine hydroxylase (TH), the first and rate-limiting enzyme of catecholamine biosynthetic pathway, in the dopaminergic neuronal type. In these mice, TH expression in noradrenergic and adrenergic cells was restored. Lack of TH expression in dopaminergic neurons resulted in a marked reduction of dopamine accumulation. This led to multiple behavioral abnormalities at the juvenile stage, which were characterized by a reduction in spontaneous locomotor activity, blockade of methamphetamine-induced hyperactivity, cataleptic behavior, and defect in active avoidance learning. In contrast, development of pituitary gland as well as production and secretion of the pituitary peptide hormones dependent on hypothalamic dopaminergic control were normally maintained in spite of the reduced dopamine synthesis. Our findings provide genetic evidence that dopamine is essential for controlling spontaneous and voluntary movement and emotional learning during postnatal development through the nigrostriatal and mesocorticolimbic pathways.
Kobayashi
K
K
Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical, University School of Medicine, 960-1297, Fukushima, Japan. kazuto@fmu.ac.jp
Sano
H
H
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000002:abnormalities / Q000201:enzymology / Q000254:growth & development; D004298:Dopamine / Q000172:deficiency* / Q000235:genetics*; D006128:Growth / Q000502:physiology; D007859:Learning Disabilities / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic / Q000002:abnormalities* / Q000254:growth & development / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics; D010902:Pituitary Gland / Q000002:abnormalities / Q000254:growth & development / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000235:genetics
D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine