Regulation of psychomotor functions by dopamine: integration of various approaches.

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  • SASA Masashi
    Nagisa Hospital
  • NISHI Akinori
    Department of Physiology, Kurume University School of Medicine
  • KOBAYASHI Kazuto
    Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University
  • SANO Hiromi
    Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University
  • MOMIYAMA Toshihiko
    Division of Cerebral Structure, National Institute for Physiological Sciences
  • URAMURA Kazuhide
    Department of Neuropsychiatry, Faculty of Medicine, Kagoshima University
  • YADA Toshihiko
    Department of Physiology, Jichi Medical School
  • MORI Norio
    Department of Psychiatry & Neurology, Hamamatsu University School of Medicine
  • SUZUKI Katsuaki
    Department of Psychiatry & Neurology, Hamamatsu University School of Medicine
  • MINABE Yoshio
    Department of Psychiatry & Neurology, Hamamatsu University School of Medicine

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Other Title
  • 薬理学のＱＯＬへの貢献　　３　　ドパミンによる運動精神機能調節：新たな研究への展開
  • ドパミンによる運動精神機能調節:新たな研究への展開
  • ドパミン ニ ヨル ウンドウ セイシン キノウ チョウセツ アラタ ナ ケンキュウ エ ノ テンカイ

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(1)The basal ganglia circuitry mediates a wide rage of brain functions such as motor control, behavioral planning, and reward prediction. Dopamine (DA) transmission plays an essential role in the regulation of these brain functions. DA action not only regulates the firing activity of target neurons but also is involved in the pattern formation of their firing. The striatopallidal neurons containing dopamine D2 receptor plays a dual role in motor coordination dependent on DA transmission. (2)Activation of presynaptic D2-like receptors on GABAergic terminals onto striatal cholinergic interneurons selectively blocks N-type Ca2+ channels, thereby inhibiting GABA release. In addition, contribution of N-type channels and D2-like receptor-mediated presynaptic inhibition decreases in parallel with development, implying some relationship between basal ganglia-related function or dysfunction and age. (3)As an approach to determine dopamine neuronal activity, we monitored neuronal activities by measuring cytosolic Ca2+ concentration in VTA dopamine neurons. The present study indicates that VTA dopamine neurons are the direct targets of orexin-A and psychostimulants, and the [Ca2+]i signaling is thought to play a significant role in the regulation of dopamine neuronal activity. (4)The excitability of neostriatal neurons is regulated by a balance of glutamatergic and dopaminergic inputs. Glutamate has been shown to modulate dopaminergic signaling. Studies on the regulation of DARPP-32 phosphorylation by glutamate provide a molecular basis for both the synergistic and antagonistic effects of glutamate on dopaminergic signaling. (5) Impairment of function of stem/progenitor cells may be implicated in the pathogenesis of schizophrenia. To test this hypothesis, several experiments are currently ongoing in our laboratory, and the preliminary results obtained are described here.<br>

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