Effect of Selective Serotonin Reuptake Inhibitors via 5-HT<SUB>1A</SUB> Receptors on L-DOPA-Induced Rotational Behavior in a Hemiparkinsonian Rat Model
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概要
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L-Dihydroxyphenylalanine (L-DOPA) is considered the gold standard for the treatment of Parkinson’s disease (PD). However, long-term administration of L-DOPA can induce abnormal side effects. On the other hand, selective serotonin reuptake inhibitors (SSRIs) including fluoxetine have gained tremendous popularity in the treatment of depression in PD. SSRIs are thought to influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic networks, which are complex and not yet fully understand. In this study, intranigral injection of 6-hydroxydopamine (6-OHDA) in rats caused a significant loss of tyrosine hydroxylase immunoreactivity in the striatum and substantia nigra. However, tryptophan hydroxylase immunoreactivity of the striatum and raphe nucleus was unaffected by 6-OHDA. Immunohistochemical analysis reveal that the serotonergic system was unaffected by the injection of 6-OHDA. We demonstrated also that pre-treatment with fluoxetine significantly suppressed L-DOPA-induced rotational behavior. Additionally, fluoxetine suppressed L-DOPA-induced ERK1/2 and histone H3 phosphorylation. These effects of fluoxetine were abolished by pre-treatment with WAY 100135, a 5-HT<SUB>1A</SUB> antagonist. These results suggest that fluoxetine may influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic neuronal networks.
- 公益社団法人 日本薬理学会の論文
著者
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Takata Kazuyuki
Department Of Mechanical Engineering Aichi Institute Of Technology
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Inden Masatoshi
Department Of Neurobiology And 21st Century Coe Program Kyoto Pharmaceutical University
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Kitamura Yoshihisa
Department Of Neurobiology Kyoto Pharmaceutical University
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Abe Mari
Department Of Biological Science Faculty Of Science Hiroshima University
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Tooyama Ikuo
Molecular Neuroscience Research Center Shiga University Of Medical Science
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Yoshimoto Kanji
Department Of Forensic Medicine Kyoto Prefectural University Of Medicine
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Minamino Hideaki
Department Of Neurobiology Kyoto Pharmaceutical University
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Abe Mari
Department Of Neurobiology Kyoto Pharmaceutical University
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