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Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

Content Provider	PubMed Central
Author	Kobayashi, Katsunori Haneda, Eisuke Higuchi, Makoto Suhara, Tetsuya Suzuki, Hidenori
Copyright Year	2012
Abstract	The dentate gyrus of the hippocampus has been implicated in mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). We have recently demonstrated that the SSRI fluoxetine can reverse the state of maturation of the adult dentate granule cells and enhances serotonin 5-HT4 receptor-mediated synaptic potentiation at the synapses formed by their mossy fiber axons. Here, we show that fluoxetine can induce long-lasting enhancement of dopaminergic modulation at the mossy fiber synapse. Synaptic responses arising from the mossy fiber-CA3 pyramidal cell synapse were recorded using acute mouse hippocampal slices. Dopamine potentiates mossy fiber synaptic transmission by activating D1-like receptors. Chronic fluoxetine treatment induced a prominent increase in the magnitude of dopamine-induced synaptic potentiation, and this effect was maintained at least up to 1 month after withdrawal of fluoxetine. Quantitative autoradiography revealed that binding of the D1-like receptor ligand [3H]SCH23390 was selectively increased in the dentate gyrus and along the mossy fiber in fluoxetine-treated mice. However, binding of the 5-HT4 receptor ligand [3H]GR113808 was not significantly changed. These results suggest that chronic fluoxetine enhanced the dopaminergic modulation at least in part by upregulating expression of D1-like receptors, while the enhanced serotonergic modulation may be mediated by modifications of downstream signaling pathways. These enhanced monoaminergic modulations would greatly increase excitatory drive to the hippocampal circuit through the dentate gyrus. The highly localized upregulation of D1-like receptors further supports the importance of the dentate gyrus in the mechanism of action of SSRIs.
Related Links	http://dx.doi.org/10.1038/npp.2011.335
Ending Page	1508
Page Count	9
Starting Page	1500
File Format	PDF
ISSN	0893133X
e-ISSN	1740634X
Journal	Neuropsychopharmacology
Issue Number	6
Volume Number	37
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-05-01
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology Psychiatry and Mental Health

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