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Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant action of a selective serotonin reuptake inhibitor, fluoxetine

Title
Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant action of a selective serotonin reuptake inhibitor, fluoxetine
Authors
Shuto, TakahideKuroiwa, MahomiSotogaku, NaokiKawahara, YukieOh, Yong-SeokJang, Jin-HyeokShin, Chang HunOhnishi, YoshinoriHanada, YuukiMiyakawa, TsuyoshiKim, YongGreengard, PaulNishi, Akinori
DGIST Authors
Oh, Yong-Seok; Jang, Jin-Hyeok
Issue Date
2018-12
Citation
Molecular Psychiatry
Type
Article
Article Type
Article in Press
ISSN
1359-4184
Abstract
Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches. Here, we demonstrate that dopamine D1 receptors in the dentate gyrus act as a pivotal mediator of antidepressant actions in mice. Chronic administration of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, increases D1 receptor expression in mature granule cells in the dentate gyrus. The increased D1 receptor signaling, in turn, contributes to the actions of chronic fluoxetine treatment, such as suppression of acute stress-evoked serotonin release, stimulation of adult neurogenesis and behavioral improvement. Importantly, under severely stressed conditions, chronic administration of a D1 receptor agonist in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression and behavioral responses. Thus, our results suggest that stimulation of D1 receptors in the dentate gyrus is a potential adjunctive approach to improve therapeutic efficacy of SSRI antidepressants. © 2018, The Author(s).
URI
http://hdl.handle.net/20.500.11750/9482
DOI
10.1038/s41380-018-0316-x
Publisher
Nature Publishing Group
Related Researcher
  • Author Oh, Yong-Seok Molecular Psychiatry Lab
  • Research Interests Monoaminergic regulation of the CNS and mood;anxiety disorder; 모노아민 (세로토닌, 도파민)에 의한 신경조절과 기분;불안 장애 기전 연구
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Collection:
Department of Brain and Cognitive SciencesMolecular Psychiatry Lab1. Journal Articles
Department of Brain and Cognitive SciencesETC1. Journal Articles


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