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

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)450-464
Number of pages15
JournalJournal of Neuroscience Research
Volume54
Issue number4
DOIs
Publication statusPublished - 15-11-1998

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Tyrosine 3-Monooxygenase
Dopamine
Learning
Knockout Mice
Avoidance Learning
Multiple Abnormalities
Problem-Based Learning
Pituitary Hormones
Methamphetamine
Peptide Hormones
Biosynthetic Pathways
Pituitary Gland
Locomotion
Mixed Function Oxygenases
Transgenes
Synaptic Transmission
Epinephrine
Catecholamines
Norepinephrine
Phenotype

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

Nishii, Kazuhiro ; Matsushita, Natsuki ; Sawada, Hirohide ; Sano, Hiromi ; Noda, Yukihiro ; Mamiya, Takayoshi ; Nabeshima, Toshitaka ; Nagatsu, Ikuko ; Hata, Tadayoshi ; Kiuchi, Kazutoshi ; Yoshizato, Hideo ; Nakashima, Kunio ; Nagatsu, Toshiharu ; Kobayashi, Kazuto. / Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission. In: Journal of Neuroscience Research. 1998 ; Vol. 54, No. 4. pp. 450-464.
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abstract = "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.",
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Nishii, K, Matsushita, N, Sawada, H, Sano, H, Noda, Y, Mamiya, T, Nabeshima, T, Nagatsu, I, Hata, T, Kiuchi, K, Yoshizato, H, Nakashima, K, Nagatsu, T & Kobayashi, K 1998, 'Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission', Journal of Neuroscience Research, vol. 54, no. 4, pp. 450-464. https://doi.org/10.1002/(SICI)1097-4547(19981115)54:4<450::AID-JNR3>3.0.CO;2-B

Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission. / Nishii, Kazuhiro; Matsushita, Natsuki; Sawada, Hirohide; Sano, Hiromi; Noda, Yukihiro; Mamiya, Takayoshi; Nabeshima, Toshitaka; Nagatsu, Ikuko; Hata, Tadayoshi; Kiuchi, Kazutoshi; Yoshizato, Hideo; Nakashima, Kunio; Nagatsu, Toshiharu; Kobayashi, Kazuto.

In: Journal of Neuroscience Research, Vol. 54, No. 4, 15.11.1998, p. 450-464.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Motor and learning dysfunction during postnatal development in mice defective in dopamine neuronal transmission

AU - Nishii, Kazuhiro

AU - Matsushita, Natsuki

AU - Sawada, Hirohide

AU - Sano, Hiromi

AU - Noda, Yukihiro

AU - Mamiya, Takayoshi

AU - Nabeshima, Toshitaka

AU - Nagatsu, Ikuko

AU - Hata, Tadayoshi

AU - Kiuchi, Kazutoshi

AU - Yoshizato, Hideo

AU - Nakashima, Kunio

AU - Nagatsu, Toshiharu

AU - Kobayashi, Kazuto

PY - 1998/11/15

Y1 - 1998/11/15

N2 - 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.

AB - 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.

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