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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- Inden Masatoshi
- Department of Neurobiology, Kyoto Pharmaceutical University, Japan
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- Abe Mari
- Department of Neurobiology, Kyoto Pharmaceutical University, Japan
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- Minamino Hideaki
- Department of Neurobiology, Kyoto Pharmaceutical University, Japan
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- Takata Kazuyuki
- Department of Neurobiology, Kyoto Pharmaceutical University, Japan
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- Yoshimoto Kanji
- Department of Legal Medicine, Kyoto Prefectural University of Medicine, Japan
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- Tooyama Ikuo
- Molecular Neuroscience Research Center, Shiga University of Medical Science, Japan
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- Kitamura Yoshihisa
- Department of Neurobiology, Kyoto Pharmaceutical University, Japan
Bibliographic Information
- Other Title
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- Effect of Selective Serotonin Reuptake Inhibitors via 5-HT1A Receptors on L-DOPA-Induced Rotational Behavior in a Hemiparkinsonian Rat Model
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Abstract
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-HT1A antagonist. These results suggest that fluoxetine may influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic neuronal networks.
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 119 (1), 10-19, 2012
The Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390282680155023488
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- NII Article ID
- 10030760133
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- NII Book ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC38XnvVKnsrs%3D
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 023634642
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- PubMed
- 22510520
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed