Synergistic Effects of Adenosine A2A Antagonist and <sc>L</sc>-DOPA on Rotational Behaviors in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Mouse Model
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概要
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In this study, we examined the combination effects of <sc>L</sc>-DOPA and adenosine receptor antagonists on rotational behaviors in a hemi-Parkinsonian mouse model induced by unilateral 6-hydroxydopamine (6-OHDA) injection. The adenosine A2A antagonist SCH-58261, but not the A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or A2B-receptor antagonist alloxazine, synergistically potentiated the <sc>L</sc>-DOPA-induced rotational behaviors in the 6-OHDA-lesioned mice. In addtion, the 6-OHDA-induced lesions of the dopaminergic system did not affect the in vivo binding of an adenosine A2A-receptor tracer [11C]SCH-442416 in the striatatum. These findings suggest that adenosine A2A antagonists are extremely useful for pharmacotherapy of <sc>L</sc>-DOPA in Parkinson’s disease patients.
著者
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Yamada Kiyofumi
Laboratory Of Experimental Therapeutics Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sc
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ASAI Makoto
Basic Research Division, The Medical and Pharmacological Research Center Foundation
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MIYOSHI Sosuke
Basic Research Division, The Medical and Pharmacological Research Center Foundation
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NAGAI Taku
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science
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MIZOGUCHI Hiroyuki
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science
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Nishimura Shintaro
Basic Research Division The Medical And Pharmacological Research Center Foundation
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Matsuya Takahiro
Laboratory Of Neuropsychopharmacology Division Of Life Sciences Graduate School Of Natural Science A
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Noda Akihiro
Basic Research Division The Medical And Pharmacological Research Center Foundation
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Murakami Yoshihiro
Basic Research Division The Medical And Pharmacological Research Center Foundation
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Sato Kosuke
Laboratory Of Neuropsychopharmacology Division Of Life Sciences Graduate School Of Natural Science A
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Takuma Kazuhiro
Laboratory Of Medicinal Pharmacology Graduate School Of Pharmaceutical Sciences Osaka University
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Yamada Kiyofumi
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Japan
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Nagai Taku
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Japan
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Noda Akihiro
Basic Research Division, The Medical and Pharmacological Research Center Foundation, Japan
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Matsuya Takahiro
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Japan
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Mizoguchi Hiroyuki
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Japan
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Asai Makoto
Basic Research Division, The Medical and Pharmacological Research Center Foundation, Japan
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Nishimura Shintaro
Basic Research Division, The Medical and Pharmacological Research Center Foundation, Japan
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