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

Takahide Shuto, Mahomi Kuroiwa, Naoki Sotogaku, Yukie Kawahara, Yong Seok Oh, Jin Hyeok Jang, Chang Hoon Shin, Yoshinori N. Ohnishi, Yuuki Hanada, Tsuyoshi Miyakawa, Yong Kim, Paul Greengard, Akinori Nishi

研究成果: Article

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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.

元の言語English
ページ(範囲)1229-1244
ページ数16
ジャーナルMolecular Psychiatry
25
発行部数6
DOI
出版物ステータスPublished - 01-06-2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Shuto, T., Kuroiwa, M., Sotogaku, N., Kawahara, Y., Oh, Y. S., Jang, J. H., Shin, C. H., Ohnishi, Y. N., Hanada, Y., Miyakawa, T., Kim, Y., Greengard, P., & Nishi, A. (2020). Obligatory roles of dopamine D1 receptors in the dentate gyrus in antidepressant actions of a selective serotonin reuptake inhibitor, fluoxetine. Molecular Psychiatry, 25(6), 1229-1244. https://doi.org/10.1038/s41380-018-0316-x