| Aripiprazole differentially affects mesolimbic and nigrostriatal dopaminergic transmission: implications for long-term drug efficacy and low extrapyramidal side-effects. | |
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MedLine Citation:
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PMID: 19203411 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Aripiprazole has been used effectively to treat schizophrenia in the clinic; however, its mechanisms of action are not clear. This study examined how short- and long-term aripiprazole treatment affects dopaminergic transmission in mesolimbic and nigrostriatal pathways. For comparison, the effects of haloperidol and olanzapine treatment were also examined. Aripiprazole significantly increased D2 receptor mRNA expression and decreased tyrosine hydroxylase (TH) mRNA expression in the ventral tegmental area (VTA) after 1- and 12-wk treatment, but had no effect in substantia nigra (SN) and nucleus accumbens (NAc). Aripiprazole also decreased dopamine transporter (DAT) binding density in NAc (for 1- and 12-wk treatment) and VTA (1-wk treatment). In contrast, haloperidol significantly increased D2 receptor binding density and decreased DAT binding density in NAc and caudate putamen (CPu) after 1- and 12-wk treatment, and it also decreases DAT binding in VTA after 12-wk treatment. Olanzapine had less widespread effects, namely an increase in D2 receptor mRNA in VTA after 12-wk treatment and decreased DAT binding in NAc after 1-wk treatment. These results suggest that aripiprazole has selective effects on the mesolimbic dopaminergic pathway. Selectively reducing dopamine synthesis in VTA is a possible therapeutic mechanism for the long-term efficacy of aripiprazole in controlling schizophrenia symptoms with reduced extrapyramidal side-effects. |
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Authors:
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Mei Han; Xu-Feng Huang; Chao Deng |
Publication Detail:
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Type: Journal Article Date: 2009-02-10 |
Journal Detail:
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Title: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) Volume: 12 ISSN: 1469-5111 ISO Abbreviation: Int. J. Neuropsychopharmacol. Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2011-05-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815893 Medline TA: Int J Neuropsychopharmacol Country: England |
Other Details:
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Languages: eng Pagination: 941-52 Citation Subset: IM |
Affiliation:
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Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Wollongong, NSW, Australia. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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